Open Access

Tumour‑derived exosomes and their emerging roles in leukaemia (Review)

  • Authors:
    • Lei Chen
    • Ting Xie
    • Bing Wei
    • Da-Lin Di
  • View Affiliations

  • Published online on: February 6, 2023
  • Article Number: 126
  • Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Exosomes are small vesicles with a diameter of ~40‑100 nm that are secreted by the majority of endogenous cells under normal and pathological conditions. They contain abundant proteins, lipids, microRNAs, and biomolecules such as signal transduction molecules, adhesion factors and cytoskeletal proteins, and play an important role in exchanging materials and transmitting information between cells. Recent studies have shown that exosomes are involved in the pathophysiology of leukaemia by affecting the bone marrow microenvironment, apoptosis, tumour angiogenesis, immune escape and chemotherapy resistance. Furthermore, exosomes are potential biomarkers and drug carriers for leukaemia, impacting the diagnosis and treatment of leukaemia. The present study describes the biogenesis and general characteristics of exosomes, and then highlight the emerging roles of exosomes in different types of leukaemia. Finally, the value of clinical application of exosomes as biomarkers and drug carriers is discussed with the aim to provide novel strategies for the treatment of leukaemia.

1. Introduction

Leukaemia is a common cancer of the haematopoietic system, whose pathogenesis has not been fully elucidated. Leukaemia cells are stagnant in different stages of cell development due to uncontrolled proliferation, impaired differentiation and blocked regulation. They proliferate massively in the bone marrow and other haematopoietic tissues and infiltrate other non-haematopoietic tissues and organs, and these processes are multifactorial and multistage. According to the French-American-British classification standard, leukaemia is divided into four categories: Acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), chronic lymphocytic leukaemia (CLL) and chronic myeloid leukaemia (CML). If left untreated, these conditions may lead to bone marrow failure and eventual death, and only a few patients are cured, even with the best treatments such as intensive chemotherapy or haematopoietic stem cell (HSC) transplantation (1). With the improvement of treatment technology, especially the progress of HSC transplantation in recent years, the remission rate of patients with leukaemia has been improved, but the majority of patients still experience relapse after remission according to the World Health Organization (WHO) (2).

Exosomes were first discovered in sheep reticulocytes in the 1980s (3). Sheep reticulocytes release vesicles during in vitro culture, and the externalization of vesicles was hypothesized to be a specific membrane shedding mechanism, which Johnstone et al (4) named ‘exosomes’ in 1987. Exosomes are vesicles with a diameter of 40-100 nm secreted by living cells under normal and pathological conditions. They have a typical lipid bilayer structure and contain abundant amounts of proteins, lipids, mRNAs or microRNAs (miRNAs/miRs) and present abundantly in the plasma, urine and ascites. They also play important physiological and pathological roles by interacting with neighbouring or distant cells (5,6). Exosomes mediate the exchange of biological information between cells, which is an important method for tumour cells to transmit information to the outside environment, widely involved in tumour cell proliferation, local invasion and distant metastasis (7,8). Recent evidence indicates that exosomes potential impact the occurrence and development of leukaemia by regulating the bone marrow microenvironment, tumour cell apoptosis, angiogenesis and immune escape (9). The present manuscript aimed to introduce the role of exosomes in the pathogenesis of leukaemia and provide novel strategies for treating leukaemia clinically.

2. Formation and release of exosomes

Extracellular vesicles (EV) are lipid bimolecular membrane vesicles released by cells into the extracellular microenvironment that play an important role in intercellular communication, and also participate in various physiological and pathological body processes. EVs are divided into exosomes, apoptotic bodies, microvesicles and large oncosomes according to their different formation methods. For example, exosomes can be released by almost all cells, transferred to target cells through cell-to-cell communication, and perform numerous biological functions (10). Recently, there has been an increase in research into exosomes, especially in the medical field. The formation of exosomes is a continuous process involving sorted endosomes, intraluminal vesicles (ILV) and intracellular multivesicular bodies (MVB). The cell membrane is invaginated to form a goblet structure when stimulated by microbial attack or stress conditions. Extracellular material or membrane proteins are internalized and form early-sorting endosomes (ESEs), the extracellular cargo enters the cell by cell membrane internalization (for example, via phagocytosis) (11). To participate in the assembly of exosomes, some cargo may enter the cell more efficiently with the help of receptors expressed on the cell membrane. Ubiquitinated molecules such as proteins or RNAs bind to ESEs with the assistance of sorting proteins, and the ESEs gradually mature into late-sorting endosomes (LSEs). ILVs in LSEs are the precursors of exosomes, and LSEs eventually evolve into MVBs. Occasionally, MVBs are degraded after fusion with lysosomes. Or, MVBs fuse with the plasma membrane to release ILVs into the extracellular environment, which are exosomes. Exosomes affect the function of target cells through endocytosis or ligand-receptor recognition (12). The formation process of exosomes is presented in Fig. 1.

Exosome-mediated intercellular communication regulates normal physiological activities between cells and is also widely involved in the pathological process of numerous diseases, including tumorigenesis. Generally, tumour cells can produce more exosomes compared with normal cells, and these tumour-derived exosomes manifest multiple abilities to change the local and distant microenvironment, which contributes to tumorigenesis, metastasis and immune escape (13). Common methods for collecting exosomes from body fluids such as urine, bronchoalveolar lavage fluid, serum and ascites of patients with tumours include ultracentrifugation, ultrafiltration and commercial kits. Each method has advantages and disadvantages. Only the extracted exosomes with high purity, concentration and content while avoiding heterologous protein interference can meet the requirements of subsequent research (14). With the rapid development of modern medical technology, advanced technologies, such as biophysical techniques based on spectroscopy (scanning electron microscopy, atomic force microscopy), and antibody-based techniques (flow cytometry, transmission electron microscopy) can be used to characterise and identified various exosomes (15). A paper-based isotachophoresis technique enables rapid identification of exosomes from healthy cells or tumour cells, and this technique can sensitively detect exosomes down to 2.0-3.0x10-18 M with potential clinical application value (16).

3. Regulatory effect of exosomes on bone marrow microenvironment

The bone marrow microenvironment (BMM) is the basis for the survival of HSCs (17). Increasing evidence indicates that tumour-derived exosomes can remodel the BMM to a leukaemia-favourable microenvironment through the communication of biological information between HSCs and tumour cells (18,19).


The pathogenesis of AML involves a tumour cell favourable BMM, which supports the formation and progression of leukaemia cells, and for exosomes to inhibit the haematopoiesis function of bone marrow through the targeted delivery of miRNAs to haematopoietic progenitor cells (20). AML-derived exosomes that contain coding and non-coding RNAs phagocytosed by bone marrow stromal cells (BMSCs) can promote tumour cell growth by stimulating the secretion of growth factors (21). AML-derived exosomes containing miRNAs that downregulate the expression of retention factors, such as stem cell factor and C-X-C chemokine ligand 12 (CXCL12), in BMSCs may disrupt the haematopoietic function of the bone marrow (22).

AML-derived exosomes inhibit the expression of haematopoietic factor Dickkopf-related protein 1 (DKK1) and HSC support factors, such as CXCL12, kit ligand and insulin-like growth factor I, in the bone marrow. This forms a favourable tumour cell microenvironment and impairs the haematopoiesis ability of bone marrow (23). The loss of the haematopoiesis ability in patients with AML is partly attributable to AML-derived exosomes transporting miRNAs to HSPCs, which inhibit the C-MYB gene function through miR-150 and miR-155, and inhibit the clonogenic ability of myeloid cells (24). Exosomes containing miR-4532 released by AML cells interact with HSCs and impair the clonogenic ability of HSCs through the JAK2 and STAT3 signalling pathways, inhibiting bone marrow haematopoiesis by increasing the expression of haematopoietic inhibitor DKK1(25). Exosomes containing miR-7977 released by AML cells can enhance the proliferation ability of BMSCs through the Hippo-YAP signalling pathway, which may be involved in the upregulation of leukaemia-supporting stroma growth (26). A recent study confirmed that the expression level of miR-425-5p is reduced in patients with CD34+CD38- AML, and exosomes containing miR-425-5p derived from the BMSCs of these patients can inhibit AML cell proliferation, invasion and migration through the Wilms tumour 1 associated protein pathway, this indicates that miR-425-5p may be a potential therapeutic target for patients with AML (27).


Tumour-derived exosomes are important messengers in leukaemia that remodel the BMM into a malignant ecology to improve support for ALL cell survival through inflammatory cytokines, chemokines and adhesion molecules. Abnormal production of inflammatory mediators in bone marrow may reduce the normal function of HSCs during the tumorigenesis of ALL. Exosomes secreted by tumour cells contain miRNAs, such as miR-146a-5p, miR-181b-5p and miR-199b-3p, that bind to Toll-like receptor (TLR)8 on the surface of bone marrow mesenchymal stromal cells (BM-MSCs). This activates inflammatory pathways and remodels the tumour microenvironment (TME) through TLR8 signalling, significantly reducing the haematopoietic capacity of normal HSCs and promoting the progression of ALL (28,29).


The pathogenesis of CLL is closely associated with the BMM, which supports tumour cell growth and a dysfunctional immune system. The interaction of BMSCs with CLL-derived exosomes induces the expression of a cancer-associated fibroblast phenotype, and exosome-stimulated BMSCs exhibit an enhanced proliferation and inflammatory cytokine secretion ability. This is favourable for creating a microenvironment that supports tumour cell survival (30). Furthermore, the endocytosis of exosomes by endothelial cells increases angiogenesis in vitro and in vivo and promotes tumour cell metastasis (31). A study suggested that B cell receptor (BCR) signalling can promote CLL pathogenesis and tumour cell survival. MiR-150 and miR-155 expression levels are significantly elevated in CLL-derived exosomes by α-IgM stimulation, promoting disease progression; however, the tyrosine kinase inhibitor (TKI) ibrutinib may offset this effect (32). CLL-derived exosomes regulate the dynamic interaction between tumour cells and the bone marrow microenvironment, and regulate the TME through NF-κB and the PI3K/AKT pathway, providing support for the pathogenesis of CLL (33).


Exosomes released by CML cells stimulate BMSCs to produce pro-inflammatory chemokines, such as IL-8, that promote the expression of malignant phenotypes of CML cells through C-X-C chemokine receptor signalling (34). Exosomes released from CML cells contain miRNAs that promote the formation of the TME. Among the 124 miRNAs identified from the CML cell line LAMA84, miR-126 can down-regulate the expression levels of chemokine CXCL-12 and vascular cell adhesion molecule-1 (VCAM-1) in endothelial cells, This impairs the adherence of tumour cells to endothelial cells, which may facilitate tumour cell migration from the bone marrow and dissemination in vivo (35).

A recent study showed that K562 cell-derived exosomes transfer miR-711 into BMSCs, inhibiting the adhesion ability of BMSCs by down-regulating CD44 molecule expression. There is a significantly higher level of miR-711 in exosomes derived from K562 cells compared with exosomes derived from parental cells (36). The BM-MSCs co-cultured with exosomes derived from K562 cells showed a lower adhesion rate, which may be associated with tumour cell metastasis. Hyperleukocytic acute leukaemia patient-derived exosomes contain miR-125b, which can reduce colony forming units and the expression of BM-MSC haematopoietic-related factors α-globulin, γ-globulin, colony-stimulating factor 2, CRTX4 and CXCL12. These results indicated that exosomes carrying miR-125b might affect the haematopoietic differentiation function of HSCs and the haematopoietic support for BM-MSCs (37).

CML-derived exosomes containing miR-320 can be endocytosed by the adjacent BMSCs and then inhibit the function of osteoblasts at least partially via β-catenin, which contributes to CML progression. Notably, β-catenin is a key regulator of osteogenesis that can promote the maturation of osteoblastic precursor cells into mature osteoblasts through Wnt signalling, the 3'-UTR of β-catenin contains a binding site that miR-320 can recognize (38). K562 cell-derived exosomes induce T cell fate to evolve toward tumour-favourable suppressor T cells instead of traditional killer T cells by promoting the expression of NAD (P)H quinone oxidoreductase 1, programmed death ligand 1 (PD-L1) and forkhead box protein P3 (FOXP3), while increasing the secretion of cytokines such as IL-10, IL-6 and IL-17(39).

Cancer-associated cachexia (CAC) impacts the quality of life of patients with CML, especially in the advanced stage. It has been confirmed that mice significantly lost weight and body fat percentage after being injected with CML-derived exosomes (40). Further research confirmed that the adipogenic ability of adipose-derived stem cells are reduced by exosomes containing miR-92a-3p, indicating that tumour-derived exosomes may be involved in the occurrence of CAC (40). The regulatory effects of exosomes on the bone marrow microenvironment are presented in Table I.

Table I

Regulatory effects of exosomes on the bone marrow microenvironment.

Table I

Regulatory effects of exosomes on the bone marrow microenvironment.

First author, yearCancer typemiRs in exosomeEffects(Refs.)
Hornick et al, 2016AMLmiR-150, miR-155Suppresses haematopoiesis of haematopoietic stem and progenitor cell(24)
Zhao et al, 2019AMLmiR-4532Decrease the clonogenic and haematopoietic function in haematopoietic stem cells(25)
Yoshida et al, 2019AMLmiR-7977Enhance the proliferation ability of bone marrow mesenchymal stem cells(26)
Zhang et al, 2021AMLmiR-425-5pInhibit AML cell proliferation, invasion migration ability, and induce cell apoptosis(27)
Rios et al, 2022ALLmiR-146a-5p, miR-181b-5p, miR-199b-3pPromotes the formation of the tumour microenvironment and reduces the haematopoietic ability of haematopoietic stem cells(29)
Yeh et al, 2015CLLmiR-150, miR-155Regulate the pathogenesis of CLL through BCR signalling(32)
Taverna et al, 2014CMLmiR-126Downregulate CXCL12 and VCAM1 expression on endothelial cells and promote leukaemia dissemination(35)
Jiang et al, 2020CMLmiR-711Suppress the adhesive function of bone marrow mesenchymal stem cells(36)
Yang et al, 2021CMLmiR-125bRegulate the haematopoietic differentiation function of HSC and the haematopoietic support function of BM-MSC(37)
Gao et al, 2019CMLmiR-320Inhibit osteoblast function and remodel the bone marrow niche(38)
Wan et al, 2019CMLmiR-92a-3pAttenuate adipogenesis of adipose-derived mesenchymal stem cells and promote CAC progression(40)

[i] AML, acute myeloid leukaemia; ALL, acute lymphoblastic leukaemia; CLL, chronic lymphocytic leukaemia; CML, chronic myeloid leukaemia; BCR, B cell receptor; VCAM-1, Vascular cell adhesion molecule 1; BM-MSC, bone marrow mesenchymal stromal cells; CAC, cancer-associated cachexia; CXCL12, chemokine (C-X-C Motif) ligand 12; miR, microRNA.

4. Effects of exosomes on proliferation and apoptosis of leukaemia cells

AML-derived miR-5195-3p can simulate tumour cell proliferation by activating the cell cycle, and can also improve the anti-apoptotic ability of tumour cells by down-regulating Bcl-2 and up-regulating Bax expression. However, AML-derived miR-23b-5p can reduce tumour cell proliferation and induce apoptosis via the PI3K/AKT pathway (41,42). BMSCs-derived miR-7-5p inhibits AML cell proliferation and promotes apoptosis through PI3K/AKT/mTOR signalling, indicating that these miRNAs may be potential therapeutic targets for AML treatment (43). BM-MSCs derived exosomes that contain miR-222-3p can inhibit AML cell line THP-1; however, these effects of BM-MSCs exosomes are reduced when the IRF2/inositol polyphosphate 4-phosphatase type II (INPP4B) signalling pathway is blocked, which suggests that BM-MSCs regulate THP-1 cells proliferation and apoptosis through IRF2/INPP4B signalling, which may provide novel therapeutic strategies for AML (44).

A study confirmed that miRNA-181b-5p is highly expressed in ALL cell lines, and exosomes carrying this miRNA can promote the proliferation, migration and invasion ability of ALL cells. MiRNA-181b-5p can also promote the progression of ALL by inhibiting cell apoptosis (45). CML-derived exosomes can promote the proliferation ability of tumour cells through TGF-β1 signalling in a CML mouse xenograft model while promoting the expression of BCL-w, BCL-xl and survivin to resist apoptosis (46). Adult T cell leukaemia/lymphoma (ATL) is a haematological disease in which lymphocytes proliferate abnormally in the bone marrow, and human T-lymphotropic virus type 1 (HTLV-1) is the causative agent. Lymphocytes will release exosomes containing viral Tax proteins, pro-inflammatory mediators and viral mRNA transcripts after being infected by HTLV-1, which can improve the survival of leukaemia cells by inhibiting Fas expression through AKT signalling, further studies confirmed that this effect depends on the anti-apoptotic protein cFLIP (47). Paediatric acute lymphoblastic leukaemia (pALL) is a malignancy of the lymphoid line of blood cells that accounts for a large percentage of all childhood leukaemia cases. Exosomes isolated from patients serum containing miR-181a, which can promote disease progression by upregulating proliferation genes (e.g. PCNA, Ki-67) and survival genes (e.g. MCL-1 and BCL2). Specific inhibition of miR-181a can reverse pALL exosome-induced proliferation function of leukaemia cells in vitro, suggesting miR-181a may be a therapeutic target for pALL (48). These findings highlight the effects of exosomes on the proliferation and apoptosis of leukaemia cells which may provide novel ideas for the treatment of leukaemia.

5. Effects of exosomes on leukaemia angiogenesis

The formation of new blood vessels contributes to the development of malignant tumours. Exosomes circulate freely in body fluids, accumulate in the TME and promote tumour angiogenesis (49). Exosomes deliver angiogenesis-promoting molecules and genetic agents to recipient cells, and are responsible for reprogramming the phenotype and function of endothelial cells in the TME, promoting leukaemia progression (50).

CML-derived exosomes stimulate vascular endothelial cell proliferation and promote the formation of new blood vessels through Src signalling in CML angiogenesis. Tyrosine kinase inhibitors dasatinib and imatinib (IM) can significantly inhibit the secretion of exosomes and the proliferation of the human umbilical cord endothelium in vitro. A further study confirmed dasatinib can attenuate angiogenesis induced by exosomes in a Matrigel mouse embolization model, CML cell-derived exosomes could induce angiogenic activity in human umbilical vein endothelial cells (HUVECs), and dasatinib manifested an inhibitory effect on exosome through Src signaling (51).

Exosomes isolated from the blood of patients with CML have been reported to contain amphiregulin which can activate the epidermal growth factor receptor signalling of BMSCs, increasing the expression of MMP-9 and IL-8, promoting the adhesion of leukaemia cells to stromal cells, supporting the development of disease (52). The progression of CML is often associated with increased angiogenesis, and CML-derived exosomes can induce the proliferation and angiogenesis of human umbilical vein endothelial cells via miR-92a (53). The exosomes secreted by K562 cells can promote the expression of VEGFR and the formation of new blood vessels, and anti-angiogenic gold nanoparticles can attenuate the pro-angiogenic effect of exosomes, highlighting nanomedicine-based potentiality to prevent the spread of leukaemia cells (54).

A hypoxic environment can regulate tumour angiogenesis. Exosomes released from K562 cells cultured in a hypoxic (1%) environment were more prone to induce tumour angiogenesis via miR-210 compared with those cultured in normoxic (20%) conditions by downregulating angiogenesis inhibitory factor ephrin-A3, which is essential for tumour cell survival in hypoxic environments (55). Exosomes secreted by K562 cells that contain miR-92a can promote tumour angiogenesis under hypoxic conditions through targeted inhibition of hypoxia-inducible factor 1 by miR-135b (56). Exosomes released from CML cells contain miR-21, which can increase expression levels of IL-8 and VCAM-1 and promote tumour angiogenesis. A vascular network formation assay confirmed that curcumin-treated exosomes induce the secretion of proteins with antiangiogenic activity and attenuate the angiogenic ability of exosomes (57). A previous study has indicated that AML-derived exosomes contain miRNAs for VEGF and VEGFR expression, promoting HUVEC cell proliferation and vascular remodelling while resisting apoptosis by promoting HUVEC cell glycolysis (58). These findings may contribute to developing novel therapeutic strategies for AML.

CLL-derived exosomes can activate the AKT signalling pathway in BMSCs following activation of cyclin D1, which produces vascular endothelial growth factor, providing a ‘homing and nurturing’ microenvironment for tumour cells and promoting CLL progress (59). Exosomes released by ATL cells containing angiogenic factors act on vascular endothelial cells to create a favourable angiogenesis microenvironment for tumour cells. Tumour cells of patients with ATL release exosomes containing miR-21, miR-155 and vascular endothelial growth factor, which interact with MSCs and induce the activation of the NF-κB signalling through Tax protein, this activates leukaemia related genes and angiogenic genes that regulate the properties of MSCs and promote leukaemia progression (60). These findings may provide novel ideas for treating haematological malignancies.

6. Effects of exosomes on tumour cell immune escape and vaccine development

The immune escape of tumour cells is one of the important reasons for the rapid progression of leukaemia. Leukaemia cells evade the supervision of the immune system by down-regulating the expression level of tumour antigens and releasing immune inhibitory cytokines to inhibit the function of lymphocytes (61).

NKG2D is a common activating receptor that is abundantly expressed on NK cells, NKT cells and CD8+ CTL cells, which plays an immune surveillance role for tumour cells, and the abnormal loss of NKG2D may be an important reason for tumour cell immune evasion (62). Exosomes secreted by tumour cells can down-regulate NKG2D expression in NK cells and CD8+ T cells while promoting the expression of TGF-β1 in tumours, creating an inhibitory immune microenvironment for tumour cell growth. Szczepanski et al (63) have confirmed that AML-derived exosomes can reduce the expression level of NKG2D and weaken the killing ability of NK cells, sera from patients with acute myeloid leukaemia contained elevated levels of TGF-β, neutralizing anti-TGF-β antibodies inhibited exosome-mediated suppression of natural killer cell activity and NKG2D down-regulation. RNA hY4 is a highly abundant non-coding RNA that is enriched in exosomes derived from the plasma of patients with CLL (64). RNA sequencing and proteomic analysis has revealed that hY4 is a driver for TLR7 signalling and promotes inflammatory cytokines such as CCL2, CCL4 and IL-6 release along with up-regulated PD-L1 expression. This contributes to tumour-associated inflammatory responses and immune escape, indicating that regulation of exosome-mediated inflammatory response may provide novel ideas for the treatment of CLL. Tumour-derived exosomes contain NKG2D ligands (MICA/B, ULBP1-6) that can bind to NKG2D competitively, impairing the monitoring ability of NK cells to tumour cells (65). AML-derived exosomes down-regulate naive CD4+ T cell activation, mediate Fas/FasL-driven T cell apoptosis, promote CD4+CD25+FOXP3+Treg cell activation and mediate tumour cell immune escape (66,67).

However, certain tumour-derived exosomes can induce specific antitumour immune responses and are expected to develop as a promising tumour vaccine. Dendritic cells (DCs) have numerous dendritic or pseudopodia-like protrusions that stretch out when they mature, and they have a powerful antigen-presenting function in the body. DC cells can recognize invading pathogens effectively, present antigens peptides to T cells and activate the adaptive immune responses, resulting in anti-pathogen immune reactions (68). Mature DCs produce exosomes that elicit potent immune activation, resulting in tumour eradication and bacterial or virus elimination. Notably, DC cells are closely associated with the pathogenesis of tumours. The CD8+ CTL-mediated immune response initiated by DCs is an important component of antitumour immunity and the basis for DC cell immunotherapy (69). In a previous study, the autologous monocytes of the patient were extracted and induced to mature DCs in vitro and loaded with tumour antigens to generate tumour antigen-loaded DCs; these DCs were then injected into the patient to activate the lymphocytes, which stimulated an antitumour immune response (70,71). The specific mechanism of DC cell immunotherapy is shown in Fig. 2. Numerous DC-based immunotherapies have been developed and have produced satisfactory treatment effects in certain clinical trials (72,73). Targeted delivery of antigens to DCs via exosomes represents a potential candidate approach for DC vaccines, which demonstrate convincing therapeutic effects in myeloma cells, liver cancer and breast cancer cells in vitro (74-76). Exosomes from TGF-β1-silenced L1210 cells (LEXTGF-β1si) can reduce the expression level of TGF-β1 in DCs and promote the maturation of DCs significantly. The matured DCs activate CD4+ T cells, and the subsequent tumour-specific CTL responses include killing responses and inflammatory responses, suggesting that targeting DCs via LEXTGF-β1si may be a promising immunotherapy strategy (77).

A previous study down-regulated PD-L1 expression in leukaemia cell exosomes using PD-L1 short hairpin RNA, and then compared the capacity of exosomes derived from PD-L1-silenced acute lymphocytic leukaemia-derived cells (LEXPD-L1si) and non-modified exosomes to induce anti-leukaemia immunity. The results confirmed that LEXPD-L1si improved DC maturation and subsequently Th cell proliferation and cytokine release while influencing the killing ability of CTL cells. The following in vivo experiments confirmed that LEXPD-L1si vaccination inhibits tumour growth and significantly prolongs the survival rate of mice (78). Exosomes can affect the antitumor ability of the body by regulating PD-L1 expression and the down-regulation of PD-L1 by exosomes induces anti-leukaemia immunity, which demonstrates the potential application of this therapy in leukaemia immunotherapy (79,80). These findings provide evidence for a novel exosome-mediated mechanism in leukaemia, and the specific effects of exosomes on tumour cell immune escape require further in-depth research.

7. Exosomes and drug resistance

Leukaemia chemotherapy resistance means leukaemia cells are insensitive or resistant to chemotherapy drugs. Drug resistance may lead to the recurrence of leukaemia and cause treatment failure, which are also the main points and difficulties of treatment for leukaemia.

Although there had been a rapid development of novel therapies for leukaemia, minimal residual disease (MRD) is still responsible for relapse and drug resistance. MRD is an obstacle to the treatment of leukaemia. Galectin-3 may play an important role in the MRD process by promoting the anti-apoptotic, colony formation and cell drug resistance abilities of tumour cells (81). Studies have confirmed that BM-MSCs can up-regulate the expression level of Galectin-3 in ALC cells, activate the Wnt/β-catenin signalling pathway and promote the progress of drug resistance in tumour cells (82). BMSCs of the B cell precursor from patients with acute lymphoblastic leukaemia (pre-B ALL) can encapsulate Galectin-3 in exosomes and deliver it to B-ALL cells, inducing drug resistance to nilotinib and vincristine by activating NF-κB signalling. Galectin-3 may be a potential target to counteract the protective effect of BMSCs on tumour cells (83).

Exosomes secreted by AML cells contain heat shock protein 70 and lysosome-associated membrane protein 3, which contribute to the interaction between AML and BMSCs. These proteins protect AML cells from apoptosis induced by the chemotherapeutic drug, etoposide, while reducing the sensitivity of AML cells to chemotherapeutic drugs by promoting the production of IL-8(84). The interaction between AML and BMSCs contributes to a protective environment for tumour cell development and resistance to chemotherapeutics (85), BMSC-secreted exosomes protect AML cells from Ara-C-induced cytotoxicity, and this chemoresistance is closely related to the decrease in nucleoside transporter activity from the cell surface. The progression of patients with AML is often accompanied by a FMS-like tyrosine kinase 3 (Flt3) mutation, and several chemotherapeutic drugs targeting FLT3 mutations have achieved satisfactory clinical treatment effects (86,87). Exosomes released by BMSCs of AML patients protect tumour cells by resistance to AC220 (a FLT3 kinase inhibitor) therapy, which is associated with miRNA-155 and miRNA-375 carried by exosomes (88). However, the specific mechanism has not been clearly understood. Another study confirmed that AML-derived exosomes containing miR-10a can target regulation of nuclear pre-MRNA domain-containing 1A and activate Wnt/β-catenin signalling to reduce the sensitivity to cytarabine of leukaemia cells (89).

BMSC-derived exosomes reduce spontaneous apoptosis of CLL cells and increase chemoresistance to fludarabine, ibrutinib, idelalisib and vegetate; in addition, the migratory capacity of CLL cells is also increased (90). Previous studies have confirmed fibroblast growth factor 2 (FGF2) is highly expressed in BMSCs and AML. Studies showed that exosomes are secreted by BMSCs containing FGF2, which are endocytosed by leukaemia cells and protect tumour cells from the chemotherapeutic agents TKIs, blocking the effects of FGF2 on stromal cells can reduce exosome release, indicting inhibition of FGF2 may be a therapeutic option for tumour resistance to TKIs (91,92). IM is a common TKI that is widely used in CML and can significantly improve the survival rate and quality of life of patients with CML. However, it has been shown that exosomes are closely associated with IM resistance; proteomic analysis of exosomes showed that 151 proteins were up-regulated and 128 proteins were down-regulated in the exosomes of patients who were IM-resistant compared with patients with CML who were IM-sensitive (93). Further bioinformatical analysis has shown that ribosomal protein RPL13 and RPL14 are notably up-regulated in IM-resistant patients with CML, and proteomic analysis of exosomes may provide novel ideas for treating IM resistance (93).

IM serves an important role in CML treatment and IM resistance is also an obstacle to CML treatment. A previous study showed that ubiquitin-specific protease is significantly up-regulated in IM-resistant clinical samples; miR-146a-5p down-regulated the IM resistance of CML, human umbilical cord mesenchymal stem cell-derived exosomes can promote IM-induced apoptosis through miR-145a-5p/USP6,indicating the potential role of miR-146a-5p in leukaemia chemoresistance (94). A study has confirmed that miR-328 is significantly decreased in IM-resistant patients, where overexpression of miR-328 sensitizes drug-resistant tumour cells to IM. By contrast, knockdown of miR-328 confers IM resistance in tumour cells, and targeting delivery exosomes can increase expression of miR-328 and increase tumour cell sensitivity to IM (95). MiR-365 in exosomes of CML cells is closely associated with IM resistance of tumour cells. CML cells that receive an exosomal delivery of miR-365 show a lower chemosensitivity and apoptosis rate, and miR-365 can induce chemoresistance in tumour cells by inhibiting the expression of pro-apoptotic proteins (96). An in vitro study has confirmed that combining exosomes secreted by human umbilical cord mesenchymal stromal cells with IM in K562 cells can enhance the expression of IM-induced Bax expression through caspase-3/9 signalling, which promotes tumour cell apoptosis and increases the sensitivity of tumour cells to IM (97). Therefore, combining IM with exosomes may be a potential strategy for tumour cell drug resistance. These findings highlight the role of exosomes in tumour cell drug resistance, and regulating miRNA expression through exosomes may provide new ideas for overcoming drug resistance in leukaemia treatment. The roles of exosomes in the pathogenesis of leukaemia are summarised in Fig. 3.

8. Exosomes as biomarkers for leukaemia

The potential function of exosomes is far beyond immunology, neurobiology, stem cell science and oncology. Notably, exosomes have a far-reaching impact on tumour cell pathogenesis, immune escape, cell proliferation and chemoresistance. For a long time, exosomes have been hypothesised to be involved in the whole process of tumour metastasis although the specific effects are still unknown and controversial (98).

In recent years, exosomes have received more attention as a promising tumour screening, diagnostic and prognostic biomarker. Bioactive molecules packaged in exosomes can promote tumour cells remodelling the microenvironment, targeting distant cells and promoting cancer metastasis. The biological agents such as miRNA in exosomes are stably and abundantly present in the body, and extracellular enzymes will not readily degrade them, this makes exosomes potentially become tumour cell biomarkers (99). Molecular and genetic analysis of exosomes in leukaemia patients may potentially provide a prognosis for patients and provide new strategies for clinical treatment (100-102). Exosomes from AML tumour cells can be used as a biomarker for AML treatment, as patients who achieved remission and survived at 3-year follow-up had significantly lower exosome levels compared with deceased patients. Therefore, specific proteins and miRNAs in exosomes can be used to trace the presence of MRD and guide doctors to adjust treatment strategies on time (103,104). Exosomes isolated from the plasma of patients with AML contain TGF-β1, which inhibits the cytotoxicity of NK cells (105). Changes in exosomes may reflect the response of a patient with AML to chemotherapy, and the exosomal profile may suggest the presence of residual disease in patients considered to have achieved complete remission. MiR-125b in AML-derived exosomes can target the BAK1 gene, inhibit tumour cell apoptosis and promote the pathogenesis of AML. The elevated miR-125b levels indicate patients are at higher risk of relapse and death, and so miR-125b levels may be a prognostic indicator for AML (106,107).

A study detected the content of exosomal miR-532 in 198 patients with AML and revealed that up-regulation of miR-532 is negatively correlated with energy metabolism such as fructose and glutamine in tumour cells. Patients with high expression of miR-532 had an improved overall survival rate, indicating that miR-532 may be used as a predictor of survival in patients with AML (108). Non-coding RNAs in exosomes support the pathogenesis of CLL, and miR-155 is overexpressed in monoclonal B lymphocytosis (MBL), which may potentially promote the transition of MBL to CLL (109). MiR-155 can be used as a biomarker for the risk of progression in individuals with MBL, as well as to identify patients with CLL who may not respond well to therapy. MiR-150 is highly expressed in CLL patients compared with healthy subjects, and the expression level of miR-150 is associated with tumour burden, disease aggressiveness and poor prognostic factors. Patients with low cellular miR-150 or patients with a high serum miR-150 level have a shorter treatment-free survival (TFS) and overall survival (OS); therefore, miR-150 may be able to monitor for disease progression as well as be an indicator for CLL prognosis (110). CML is a malignant proliferation driven by a characteristic fusion gene called BCR-ABL. The U.S. Food and Drug Administration has approved TKIs for treating CML considering their satisfactory therapeutic effect in the majority of patients (111). Monitoring BCR-ABL-derived exosomes using digital PCR after TKI therapy can identify active tumour cells and guide the follow-up treatment strategies for CML patients (112,113). These results show that exosomes can provide prognostic judgement on patients with leukaemia and new strategies for clinical treatment as an important biomarker. However, the specific mechanism remains to be further invested.

9. Exosomes as drug carriers for leukaemia

Exosomes are small intracellular membrane-based vesicles similar to the cellular components of the body, and this non-immunogenic drug delivery vehicle has advantages compared with traditional drug delivery systems, such as liposomes or nanoparticles (114). The unique biocompatibility, tissue specificity, high stability, tumour homing ability and tuneable targeting efficiency confer exosomes as an attractive drug delivery system with potential application in tumour therapy (115). BCR-ABL fusion protein promotes CML pathogenesis and IM is a selective inhibitor of BCR-ABL; exosomes loaded with IM or BCR-ABL siRNA can target CML cells and inhibit cancer cell growth by interacting with IL-3 receptors on tumour cell surface, alleviating drug resistance and adverse reactions during treatment (116). Curcumin can inhibit the expression of BCR-ABL in CML cells through exosome-derived miR-21 and inhibit the growth of tumour cells, suggesting that packaging miR-21 in exosomes may contribute to the antileukemic effect of curcumin in CML (117). Tumour cell-derived exosomes carry tumour-associated antigens that can stimulate DC cell activation and induce immune responses, CD11c, MHCII and IL-12 are up-regulated in exosome-loaded DC cells and activate CD4+ T cells effectively, prolonging the survival time of WEHI-3B mice (myelomonocytic leukaemia mice) significantly, exosomes enriched from patient sera are likely to provide an optimized source of individual-specific antigens for DC loading and vaccination, considering that exosomes are abundant in the serum of tumour patients (118). High expression levels of epidermal growth factor receptor (EGFR) contribute to the rapid progression of tumours, and is involved in tumour invasion and metastasis. A novel class of exosomes called synthetic multivalent antibodies retargeted exosomes (SMART-Exos) is generated in this situation. These SMART-Exos contain two different antibodies that can simultaneously target EGFR on tumour cells and CD3 receptors on T cells. Further in-depth study confirms SMART-Exos show tight binding ability to both EGFR-expressing triple-negative breast cancer MDA-MB-468 cells and T cells, which demonstrated satisfactory antitumour activity by activating T cells to attack breast cancer cells. SMART-Exo may likely be adapted for other disease models by utilizing different types of functional antibodies (119). Cancer cell-derived exosomes were engineered to carry DOXIL (doxorubicin HCl liposome injection) and injected into HT1080 tumour-bearing nude mice. These drug-loaded exosomes showed an enhanced therapeutic effect and more effective clearance of tumour cells in mice compared with the DOXIL alone group (120). These studies provides new strategies for exosome-based targeted delivery of antitumour drugs.

10. Summary and perspectives

Increasing studies have confirmed that tumour-derived exosomes can affect the pathogenesis and development of leukaemia by affecting the bone marrow microenvironment, apoptosis, angiogenesis, chemoradiotherapy resistance and immune escape. Certain exosome-based therapies are now used for clinical or research purposes with an in-depth understanding of the physiological and pathological roles of exosomes, although exosome-related technical and regulatory issues remain to be resolved. Notably, exosomes can be used as a biomarker to monitor leukaemia progress and as a carrier to transport chemotherapeutic drugs to inhibit the development of leukaemia, demonstrating the potential of exosome-based intervention ability in leukaemia. Notably, there need to be unified standards regarding the efficiency and drug delivery of exosomes, which are the challenges exosomes face. However, in-depth research is needed on the specific mechanism of exosomes in tumour cells, such as how obtaining high-purity exosomes for treatment and accurate delivery is particularly important, and correlational research which may impact leukaemia treatment. The following study on exosomes should focus on solving the problems of tumour cell drug resistance and recurrence, considering a significant proportion of patients relapse after treatment. In conclusion, exosomes demonstrate potential value in diagnosing leukaemia and treating and monitoring disease development. Therefore, a complete understanding of the specific mechanism of exosomes in leukaemia may provide new ideas and strategies for future clinical treatment.


Not applicable.


Funding: This research was supported by the Shandong Province Health Department (grant nos. 2019WS589 and 2017WS407) and Shandong Province Traditional Chinese Medicine Science and Technology Development Plan (grant no. 2017-216).

Availability of data and materials

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Authors' contributions

DLD conceived and designed this review. LC and TX wrote the first draft. BW participated in writing of the manuscript. All authors read and approved the final manuscript. Data authentication is not applicable.

Ethics approval and consent to participate

Not applicable.

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.



Juliusson G and Hough R: Leukemia. Prog Tumor Res. 43:87–100. 2016.PubMed/NCBI View Article : Google Scholar


Alsobhi E, Farahat F, Daghistani M, Awad K, Al-Zahran O, Al-Saiari A and Koshak F: Overall survival of adult acute myeloid leukemia based on cytogenetic and molecular abnormalities during 5 years in a single center study. Saudi Med J. 40:1171–1176. 2019.PubMed/NCBI View Article : Google Scholar


Schubert D: A brief history of adherons: The discovery of brain exosomes. Int J Mol Sci. 21(7673)2020.PubMed/NCBI View Article : Google Scholar


Johnstone RM, Adam M, Hammond JR, Orr L and Turbide C: Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J Biol Chem. 262:9412–9420. 1987.PubMed/NCBI


Keller S, Sanderson MP, Stoeck A and Altevogt P: Exosomes: From biogenesis and secretion to biological function. Immunol Lett. 107:102–108. 2006.PubMed/NCBI View Article : Google Scholar


Simpson RJ, Jensen SS and Lim JW: Proteomic profiling of exosomes: Current perspectives. Proteomics. 8:4083–4099. 2008.PubMed/NCBI View Article : Google Scholar


Théry C, Zitvogel L and Amigorena S: Exosomes: Composition, biogenesis and function. Nat Rev Immunol. 2:569–579. 2002.PubMed/NCBI View Article : Google Scholar


Skog J, Würdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, Curry WT Jr, Carter BS, Krichevsky AM and Breakefield XO: Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 10:1470–1476. 2008.PubMed/NCBI View Article : Google Scholar


Mardani R, Jafari Najaf Abadi MH, Motieian M, Taghizadeh-Boroujeni S, Bayat A, Farsinezhad A, Gheibi HS, Motieian M and Pourghadamyari H: MicroRNA in leukemia: Tumor suppressors and oncogenes with prognostic potential. J Cell Physiol. 234:8465–8486. 2019.PubMed/NCBI View Article : Google Scholar


Liu J, Ren L, Li S, Li W, Zheng X, Yang Y, Fu W, Yi J, Wang J and Du G: The biology, function, and applications of exosomes in cancer. Acta Pharm Sin B. 11:2783–2797. 2021.PubMed/NCBI View Article : Google Scholar


Cheng L and Hill AF: Therapeutically harnessing extracellular vesicles. Nat Rev Drug Discov. 21:379–399. 2022.PubMed/NCBI View Article : Google Scholar


De Toro J, Herschlik L, Waldner C and Mongini C: Emerging roles of exosomes in normal and pathological conditions: New insights for diagnosis and therapeutic applications. Front Immunol. 6(203)2015.PubMed/NCBI View Article : Google Scholar


Zhang L and Yu D: Exosomes in cancer development, metastasis, and immunity. Biochim Biophys Acta Rev Cancer. 1871:455–468. 2019.PubMed/NCBI View Article : Google Scholar


Lobb RJ, Becker M, Wen SW, Wong CS, Wiegmans AP, Leimgruber A and Möller A: Optimized exosome isolation protocol for cell culture supernatant and human plasma. J Extracell Vesicles. 4(27031)2015.PubMed/NCBI View Article : Google Scholar


Khatun Z, Bhat A, Sharma S and Sharma A: Elucidating diversity of exosomes: Biophysical and molecular characterization methods. Nanomedicine (Lond). 11:2359–2377. 2016.PubMed/NCBI View Article : Google Scholar


Guo S, Xu J, Estell AP, Ivory CF, Du D, Lin Y and Dong WJ: Paper-based ITP technology: An application to specific cancer-derived exosome detection and analysis. Biosens Bioelectron. 164(112292)2020.PubMed/NCBI View Article : Google Scholar


Agarwal P and Bhatia R: Influence of bone marrow microenvironment on leukemic stem cells: Breaking up an intimate relationship. Adv Cancer Res. 127:227–252. 2015.PubMed/NCBI View Article : Google Scholar


Sharma A, Khatun Z and Shiras A: Tumor exosomes: Cellular postmen of cancer diagnosis and personalized therapy. Nanomedicine (Lond). 11:421–437. 2016.PubMed/NCBI View Article : Google Scholar


Tan Z, Kan C, Wong M, Sun M, Liu Y, Yang F, Wang S and Zheng H: Regulation of malignant myeloid leukemia by mesenchymal stem cells. Front Cell Dev Biol. 10(857045)2022.PubMed/NCBI View Article : Google Scholar


Boyiadzis M and Whiteside TL: Exosomes in acute myeloid leukemia inhibit hematopoiesis. Curr Opin Hematol. 25:279–284. 2018.PubMed/NCBI View Article : Google Scholar


Huan J, Hornick NI, Shurtleff MJ, Skinner AM, Goloviznina NA, Roberts CT Jr and Kurre P: RNA trafficking by acute myelogenous leukemia exosomes. Cancer Res. 73:918–929. 2013.PubMed/NCBI View Article : Google Scholar


Huan J, Hornick NI, Goloviznina NA, Kamimae-Lanning AN, David LL, Wilmarth PA, Mori T, Chevillet JR, Narla A, Roberts CT Jr, et al: Coordinate regulation of residual bone marrow function by paracrine trafficking of AML exosomes. Leukemia. 29:2285–2295. 2015.PubMed/NCBI View Article : Google Scholar


Kumar B, Garcia M, Weng L, Jung X, Murakami JL, Hu X, McDonald T, Lin A, Kumar AR, DiGiusto DL, et al: Acute myeloid leukemia transforms the bone marrow niche into a leukemia-permissive microenvironment through exosome secretion. Leukemia. 32:575–587. 2018.PubMed/NCBI View Article : Google Scholar


Hornick NI, Doron B, Abdelhamed S, Huan J, Harrington CA, Shen R, Cambronne XA, Chakkaramakkil VS and Kurre P: AML suppresses hematopoiesis by releasing exosomes that contain microRNAs targeting c-MYB. Sci Signal. 9(ra88)2016.PubMed/NCBI View Article : Google Scholar


Zhao C, Du F, Zhao Y, Wang S and Qi L: Acute myeloid leukemia cells secrete microRNA-4532-containing exosomes to mediate normal hematopoiesis in hematopoietic stem cells by activating the LDOC1-dependent STAT3 signaling pathway. Stem Cell Res Ther. 10(384)2019.PubMed/NCBI View Article : Google Scholar


Yoshida M, Horiguchi H, Kikuchi S, Iyama S, Ikeda H, Goto A, Kawano Y, Murase K, Takada K, Miyanishi K, et al: miR-7977 inhibits the Hippo-YAP signaling pathway in bone marrow mesenchymal stromal cells. PLoS One. 14(e213220)2019.PubMed/NCBI View Article : Google Scholar


Zhang L, Khadka B, Wu J, Feng Y, Long B, Xiao R and Liu J: Bone marrow mesenchymal stem cells-derived exosomal miR-425-5p inhibits acute myeloid leukemia cell proliferation, apoptosis, invasion and migration by targeting WTAP. Onco Targets Ther. 14:4901–4914. 2021.PubMed/NCBI View Article : Google Scholar


Chiarini F, Lonetti A, Evangelisti C, Buontempo F, Orsini E, Evangelisti C, Cappellini A, Neri LM, Mccubrey JA and Martelli AM: Advances in understanding the acute lymphoblastic leukemia bone marrow microenvironment: From biology to therapeutic targeting. Biochim Biophys Acta. 1863:449–463. 2016.PubMed/NCBI View Article : Google Scholar


Rios de Los Rios J, Enciso J, Vilchis-Ordoñez A, Vázquez-Ramírez R, Ramirez-Ramirez D, Balandrán JC, Rodríguez-Martínez A, Ruiz-Tachiquín M, Pompa-Mera E, Mendoza L, et al: Acute lymphoblastic leukemia-secreted miRNAs induce a proinflammatory microenvironment and promote the activation of hematopoietic progenitors. J Leukoc Biol. 112:31–45. 2022.PubMed/NCBI View Article : Google Scholar


Yang Y, Li J and Geng Y: Exosomes derived from chronic lymphocytic leukaemia cells transfer miR-146a to induce the transition of mesenchymal stromal cells into cancer-associated fibroblasts. J Biochem. 168:491–498. 2020.PubMed/NCBI View Article : Google Scholar


Paggetti J, Haderk F, Seiffert M, Janji B, Distler U, Ammerlaan W, Kim YJ, Adam J, Lichter P, Solary E, et al: Exosomes released by chronic lymphocytic leukemia cells induce the transition of stromal cells into cancer-associated fibroblasts. Blood. 126:1106–1117. 2015.PubMed/NCBI View Article : Google Scholar


Yeh YY, Ozer HG, Lehman AM, Maddocks K, Yu L, Johnson AJ and Byrd JC: Characterization of CLL exosomes reveals a distinct microRNA signature and enhanced secretion by activation of BCR signaling. Blood. 125:3297–3305. 2015.PubMed/NCBI View Article : Google Scholar


Prieto D, Sotelo N, Seija N, Sernbo S, Abreu C, Durán R, Gil M, Sicco E, Irigoin V, Oliver C, et al: S100-A9 protein in exosomes from chronic lymphocytic leukemia cells promotes NF-κB activity during disease progression. Blood. 130:777–788. 2017.PubMed/NCBI View Article : Google Scholar


Corrado C, Raimondo S, Saieva L, Flugy AM, De Leo G and Alessandro R: Exosome-mediated crosstalk between chronic myelogenous leukemia cells and human bone marrow stromal cells triggers an interleukin 8-dependent survival of leukemia cells. Cancer Lett. 348:71–76. 2014.PubMed/NCBI View Article : Google Scholar


Taverna S, Amodeo V, Saieva L, Russo A, Giallombardo M, De Leo G and Alessandro R: Exosomal shuttling of miR-126 in endothelial cells modulates adhesive and migratory abilities of chronic myelogenous leukemia cells. Mol Cancer. 13(169)2014.PubMed/NCBI View Article : Google Scholar


Jiang YH, Liu J, Lin J, Li SQ, Xu YM, Min QH, Zhong QH, Sun F, Li J, You XH, et al: K562 cell-derived exosomes suppress the adhesive function of bone marrow mesenchymal stem cells via delivery of miR-711. Biochem Biophys Res Commun. 521:584–589. 2020.PubMed/NCBI View Article : Google Scholar


Yang Y, He H, He J, Gu X, Hu P, Zuo R and Sa Y: Hyperleukocytic acute leukemia circulating exosomes regulate HSCs and BM-MSCs. J Healthc Eng. 2021(9457070)2021.PubMed/NCBI View Article : Google Scholar


Gao X, Wan Z, Wei M, Dong Y, Zhao Y, Chen X, Li Z, Qin W, Yang G and Liu L: Chronic myelogenous leukemia cells remodel the bone marrow niche via exosome-mediated transfer of miR-320. Theranostics. 9:5642–5656. 2019.PubMed/NCBI View Article : Google Scholar


Jafarzadeh N, Gholampour MA, Alivand MR, Kavousi S, Arzi L, Rad F, Sadeghizadeh M and Pornour M: CML derived exosomes promote tumor favorable functional performance in T cells. BMC Cancer. 21(1002)2021.PubMed/NCBI View Article : Google Scholar


Wan Z, Chen X, Gao X, Dong Y, Zhao Y, Wei M, Fan W, Yang G and Liu L: Chronic myeloid leukemia-derived exosomes attenuate adipogenesis of adipose derived mesenchymal stem cells via transporting miR-92a-3p. J Cell Physiol. 234:21274–21283. 2019.PubMed/NCBI View Article : Google Scholar


Wang D, Ming X, Xu J and Xiao Y: Circ_0009910 shuttled by exosomes regulates proliferation, cell cycle and apoptosis of acute myeloid leukemia cells by regulating miR-5195-3p/GRB10 axis. Hematol Oncol. 39:390–400. 2021.PubMed/NCBI View Article : Google Scholar


Cheng H, Ding J, Tang G, Huang A, Gao L, Yang J and Chen L: Human mesenchymal stem cells derived exosomes inhibit the growth of acute myeloid leukemia cells via regulating miR-23b-5p/TRIM14 pathway. Mol Med. 27(128)2021.PubMed/NCBI View Article : Google Scholar


Jiang D, Wu X, Sun X, Tan W, Dai X, Xie Y, Du A and Zhao Q: Bone mesenchymal stem cell-derived exosomal microRNA-7-5p inhibits progression of acute myeloid leukemia by targeting OSBPL11. J Nanobiotechnology. 20(29)2022.PubMed/NCBI View Article : Google Scholar


Zhang F, Lu Y, Wang M, Zhu J, Li J, Zhang P, Yuan Y and Zhu F: Exosomes derived from human bone marrow mesenchymal stem cells transfer miR-222-3p to suppress acute myeloid leukemia cell proliferation by targeting IRF2/INPP4B. Mol Cell Probes. 51(101513)2020.PubMed/NCBI View Article : Google Scholar


Yan W, Song L, Wang H, Yang W, Hu L and Yang Y: Extracellular vesicles carrying miRNA-181b-5p affects the malignant progression of acute lymphoblastic leukemia. J Transl Med. 19(511)2021.PubMed/NCBI View Article : Google Scholar


Raimondo S, Saieva L, Corrado C, Fontana S, Flugy A, Rizzo A, De Leo G and Alessandro R: Chronic myeloid leukemia-derived exosomes promote tumor growth through an autocrine mechanism. Cell Commun Signal. 13(8)2015.PubMed/NCBI View Article : Google Scholar


Jaworski E, Narayanan A, Van Duyne R, Shabbeer-Meyering S, Iordanskiy S, Saifuddin M, Das R, Afonso PV, Sampey GC, Chung M, et al: Human T-lymphotropic virus type 1-infected cells secrete exosomes that contain Tax protein. J Biol Chem. 289:22284–22305. 2014.PubMed/NCBI View Article : Google Scholar


Haque S and Vaiselbuh SR: Silencing of exosomal miR-181a reverses pediatric acute lymphocytic leukemia cell proliferation. Pharmaceuticals (Basel). 13(241)2020.PubMed/NCBI View Article : Google Scholar


Aslan C, Maralbashi S, Salari F, Kahroba H, Sigaroodi F, Kazemi T and Kharaziha P: Tumor-derived exosomes: Implication in angiogenesis and antiangiogenesis cancer therapy. J Cell Physiol. 234:16885–16903. 2019.PubMed/NCBI View Article : Google Scholar


Ludwig N and Whiteside TL: Potential roles of tumor-derived exosomes in angiogenesis. Expert Opin Ther Targets. 22:409–417. 2018.PubMed/NCBI View Article : Google Scholar


Mineo M, Garfield SH, Taverna S, Flugy A, De Leo G, Alessandro R and Kohn EC: Exosomes released by K562 chronic myeloid leukemia cells promote angiogenesis in a Src-dependent fashion. Angiogenesis. 15:33–45. 2012.PubMed/NCBI View Article : Google Scholar


Corrado C, Saieva L, Raimondo S, Santoro A, De Leo G and Alessandro R: Chronic myelogenous leukaemia exosomes modulate bone marrow microenvironment through activation of epidermal growth factor receptor. J Cell Mol Med. 20:1829–1839. 2016.PubMed/NCBI View Article : Google Scholar


Umezu T, Ohyashiki K, Kuroda M and Ohyashiki JH: Leukemia cell to endothelial cell communication via exosomal miRNAs. Oncogene. 32:2747–2755. 2013.PubMed/NCBI View Article : Google Scholar


Roma-Rodrigues C, Fernandes AR and Baptista PV: Counteracting the effect of leukemia exosomes by antiangiogenic gold nanoparticles. Int J Nanomedicine. 14:6843–6854. 2019.PubMed/NCBI View Article : Google Scholar


Tadokoro H, Umezu T, Ohyashiki K, Hirano T and Ohyashiki JH: Exosomes derived from hypoxic leukemia cells enhance tube formation in endothelial cells. J Biol Chem. 288:34343–34351. 2013.PubMed/NCBI View Article : Google Scholar


Ohyashiki JH, Umezu T and Ohyashiki K: Exosomes promote bone marrow angiogenesis in hematologic neoplasia: The role of hypoxia. Curr Opin Hematol. 23:268–273. 2016.PubMed/NCBI View Article : Google Scholar


Taverna S, Fontana S, Monteleone F, Pucci M, Saieva L, De Caro V, Cardinale VG, Giallombardo M, Vicario E, Rolfo C, et al: Curcumin modulates chronic myelogenous leukemia exosomes composition and affects angiogenic phenotype via exosomal miR-21. Oncotarget. 7:30420–30439. 2016.PubMed/NCBI View Article : Google Scholar


Wang B, Wang X, Hou D, Huang Q, Zhan W, Chen C, Liu J, You R, Xie J, Chen P and Huang H: Exosomes derived from acute myeloid leukemia cells promote chemoresistance by enhancing glycolysis-mediated vascular remodeling. J Cell Physiol. 234:10602–10614. 2019.PubMed/NCBI View Article : Google Scholar


Ghosh AK, Secreto CR, Knox TR, Ding W, Mukhopadhyay D and Kay NE: Circulating microvesicles in B-cell chronic lymphocytic leukemia can stimulate marrow stromal cells: Implications for disease progression. Blood. 115:1755–1764. 2010.PubMed/NCBI View Article : Google Scholar


El-Saghir J, Nassar F, Tawil N and El-Sabban M: ATL-derived exosomes modulate mesenchymal stem cells: Potential role in leukemia progression. Retrovirology. 13(73)2016.PubMed/NCBI View Article : Google Scholar


Vago L and Gojo I: Immune escape and immunotherapy of acute myeloid leukemia. J Clin Invest. 130:1552–1564. 2020.PubMed/NCBI View Article : Google Scholar


Clayton A, Mitchell JP, Court J, Linnane S, Mason MD and Tabi Z: Human tumor-derived exosomes down-modulate NKG2D expression. J Immunol. 180:7249–7258. 2008.PubMed/NCBI View Article : Google Scholar


Szczepanski MJ, Szajnik M, Welsh A, Whiteside TL and Boyiadzis M: Blast-derived microvesicles in sera from patients with acute myeloid leukemia suppress natural killer cell function via membrane-associated transforming growth factor-beta1. Haematologica. 96:1302–1309. 2011.PubMed/NCBI View Article : Google Scholar


Haderk F, Schulz R, Iskar M, Cid LL, Worst T, Willmund KV, Schulz A, Warnken U, Seiler J, Benner A, et al: Tumor-derived exosomes modulate PD-L1 expression in monocytes. Sci Immunol. 2(eaah5509)2017.PubMed/NCBI View Article : Google Scholar


Chitadze G, Bhat J, Lettau M, Janssen O and Kabelitz D: Generation of soluble NKG2D ligands: Proteolytic cleavage, exosome secretion and functional implications. Scand J Immunol. 78:120–129. 2013.PubMed/NCBI View Article : Google Scholar


Whiteside TL: Immune modulation of T-cell and NK (natural killer) cell activities by TEXs (tumour-derived exosomes). Biochem Soc Trans. 41:245–251. 2013.PubMed/NCBI View Article : Google Scholar


Wieckowski EU, Visus C, Szajnik M, Szczepanski MJ, Storkus WJ and Whiteside TL: Tumor-derived microvesicles promote regulatory T cell expansion and induce apoptosis in tumor-reactive activated CD8+ T lymphocytes. J Immunol. 183:3720–3730. 2009.PubMed/NCBI View Article : Google Scholar


Santos PM and Butterfield LH: Dendritic cell-based cancer vaccines. J Immunol. 200:443–449. 2018.PubMed/NCBI View Article : Google Scholar


Yin W, Ouyang S, Li Y, Xiao B and Yang H: Immature dendritic cell-derived exosomes: A promise subcellular vaccine for autoimmunity. Inflammation. 36:232–240. 2013.PubMed/NCBI View Article : Google Scholar


Van Acker HH, Versteven M, Lichtenegger FS, Roex G, Campillo-Davo D, Lion E, Subklewe M, Van Tendeloo VF, Berneman ZN and Anguille S: Dendritic cell-based immunotherapy of acute myeloid leukemia. J Clin Med. 8(579)2019.PubMed/NCBI View Article : Google Scholar


Zhou J, Wang S, Sun K and Chng WJ: The emerging roles of exosomes in leukemogeneis. Oncotarget. 7:50698–50707. 2016.PubMed/NCBI View Article : Google Scholar


Wang Y, Xiang Y, Xin VW, Wang XW, Peng XC, Liu XQ, Wang D, Li N, Cheng JT, Lyv YN, et al: Dendritic cell biology and its role in tumor immunotherapy. J Hematol Oncol. 13(107)2020.PubMed/NCBI View Article : Google Scholar


Sabado RL, Balan S and Bhardwaj N: Dendritic cell-based immunotherapy. Cell Res. 27:74–95. 2017.PubMed/NCBI View Article : Google Scholar


Huang L, Rong Y, Tang X, Yi K, Qi P, Hou J, Liu W, He Y, Gao X, Yuan C and Wang F: Engineered exosomes as an in situ DC-primed vaccine to boost antitumor immunity in breast cancer. Mol Cancer. 21(45)2022.PubMed/NCBI View Article : Google Scholar


Lu Z, Zuo B, Jing R, Gao X, Rao Q, Liu Z, Qi H, Guo H and Yin H: Dendritic cell-derived exosomes elicit tumor regression in autochthonous hepatocellular carcinoma mouse models. J Hepatol. 67:739–748. 2017.PubMed/NCBI View Article : Google Scholar


Wang X, He L, Huang X, Zhang S, Cao W, Che F, Zhu Y and Dai J: Recent progress of exosomes in multiple myeloma: Pathogenesis, diagnosis, prognosis and therapeutic strategies. Cancers (Basel). 13(1635)2021.PubMed/NCBI View Article : Google Scholar


Huang F, Wan J, Hao S, Deng X, Chen L and Ma L: TGF-β1-silenced leukemia cell-derived exosomes target dendritic cells to induce potent anti-leukemic immunity in a mouse model. Cancer Immunol Immunother. 66:1321–1331. 2017.PubMed/NCBI View Article : Google Scholar


Huang F, Li Z, Zhang W, Li J and Hao S: Enhancing the anti-leukemia immunity of acute lymphocytic leukemia-derived exosome-based vaccine by downregulation of PD-L1 expression. Cancer Immunol Immunother. 71:2197–2212. 2022.PubMed/NCBI View Article : Google Scholar


Gabrusiewicz K, Li X, Wei J, Hashimoto Y, Marisetty AL, Ott M, Wang F, Hawke D, Yu J, Healy LM, et al: Glioblastoma stem cell-derived exosomes induce M2 macrophages and PD-L1 expression on human monocytes. Oncoimmunology. 7(e1412909)2018.PubMed/NCBI View Article : Google Scholar


Chen G, Huang AC, Zhang W, Zhang G, Wu M, Xu W, Yu Z, Yang J, Wang B, Sun H, et al: Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature. 560:382–386. 2018.PubMed/NCBI View Article : Google Scholar


Hu K, Gu Y, Lou L, Liu L, Hu Y, Wang B, Luo Y, Shi J, Yu X and Huang H: Galectin-3 mediates bone marrow microenvironment-induced drug resistance in acute leukemia cells via Wnt/β-catenin signaling pathway. J Hematol Oncol. 8(1)2015.PubMed/NCBI View Article : Google Scholar


Cheng YL, Huang WC, Chen CL, Tsai CC, Wang CY, Chiu WH, Chen YL, Lin YS, Chang CF and Lin CF: Increased Galectin-3 facilitates leukemia cell survival from apoptotic stimuli. Biochem Biophys Res Commun. 412:334–340. 2011.PubMed/NCBI View Article : Google Scholar


Fei F, Joo EJ, Tarighat SS, Schiffer I, Paz H, Fabbri M, Abdel-Azim H, Groffen J and Heisterkamp N: B-cell precursor acute lymphoblastic leukemia and stromal cells communicate through Galectin-3. Oncotarget. 6:11378–11394. 2015.PubMed/NCBI View Article : Google Scholar


Chen T, Zhang G, Kong L, Xu S, Wang Y and Dong M: Leukemia-derived exosomes induced IL-8 production in bone marrow stromal cells to protect the leukemia cells against chemotherapy. Life Sci. 221:187–195. 2019.PubMed/NCBI View Article : Google Scholar


Macanas-Pirard P, Broekhuizen R, González A, Oyanadel C, Ernst D, García P, Montecinos VP, Court F, Ocqueteau M, Ramirez P and Nervi B: Resistance of leukemia cells to cytarabine chemotherapy is mediated by bone marrow stroma, involves cell-surface equilibrative nucleoside transporter-1 removal and correlates with patient outcome. Oncotarget. 8:23073–23086. 2017.PubMed/NCBI View Article : Google Scholar


Daver N, Venugopal S and Ravandi F: FLT3 mutated acute myeloid leukemia: 2021 Treatment algorithm. Blood Cancer J. 11(104)2021.PubMed/NCBI View Article : Google Scholar


Daver N, Schlenk RF, Russell NH and Levis MJ: Targeting FLT3 mutations in AML: Review of current knowledge and evidence. Leukemia. 33:299–312. 2019.PubMed/NCBI View Article : Google Scholar


Viola S, Traer E, Huan J, Hornick NI, Tyner JW, Agarwal A, Loriaux M, Johnstone B and Kurre P: Alterations in acute myeloid leukaemia bone marrow stromal cell exosome content coincide with gains in tyrosine kinase inhibitor resistance. Br J Haematol. 172:983–986. 2016.PubMed/NCBI View Article : Google Scholar


Wu J, Zhang Y, Li X, Ren J, Chen L, Chen J and Cao Y: Exosomes from bone marrow mesenchymal stem cells decrease chemosensitivity of acute myeloid leukemia cells via delivering miR-10a. Biochem Biophys Res Commun. 622:149–156. 2022.PubMed/NCBI View Article : Google Scholar


Crompot E, Van Damme M, Pieters K, Vermeersch M, Perez-Morga D, Mineur P, Maerevoet M, Meuleman N, Bron D, Lagneaux L and Stamatopoulos B: Extracellular vesicles of bone marrow stromal cells rescue chronic lymphocytic leukemia B cells from apoptosis, enhance their migration and induce gene expression modifications. Haematologica. 102:1594–1604. 2017.PubMed/NCBI View Article : Google Scholar


Javidi-Sharifi N, Martinez J, English I, Joshi SK, Scopim-Ribeiro R, Viola SK, Edwards DT V, Agarwal A, Lopez C, Jorgens D, et al: FGF2-FGFR1 signaling regulates release of leukemia-protective exosomes from bone marrow stromal cells. Elife. 8(e40033)2019.PubMed/NCBI View Article : Google Scholar


Shah CA, Bei L, Wang H, Platanias LC and Eklund EA: The leukemia-associated Mll-Ell oncoprotein induces fibroblast growth factor 2 (Fgf2)-dependent cytokine hypersensitivity in myeloid progenitor cells. J Biol Chem. 288:32490–32505. 2013.PubMed/NCBI View Article : Google Scholar


Li MY, Zhao C, Chen L, Yao FY, Zhong FM, Chen Y, Xu S, Jiang JY, Yang YL, Min QH, et al: Quantitative proteomic analysis of plasma exosomes to identify the candidate biomarker of imatinib resistance in chronic myeloid leukemia patients. Front Oncol. 11(779567)2021.PubMed/NCBI View Article : Google Scholar


Chen X, Chen Y, Zhang M, Cheng H, Mai H, Yi M, Xu H, Yuan X, Liu S and Wen F: HucMSC exosomes promoted imatinib-induced apoptosis in K562-R cells via a miR-145a-5p/USP6/GLS1 axis. Cell Death Dis. 13(92)2022.PubMed/NCBI View Article : Google Scholar


Dong Y, Lin Y, Gao X, Zhao Y, Wan Z, Wang H, Wei M, Chen X, Qin W, Yang G and Liu L: Targeted blocking of miR328 lysosomal degradation with alkalized exosomes sensitizes the chronic leukemia cells to imatinib. Appl Microbiol Biotechnol. 103:9569–9582. 2019.PubMed/NCBI View Article : Google Scholar


Min QH, Wang XZ, Zhang J, Chen QG, Li SQ, Liu XQ, Li J, Liu J, Yang WM, Jiang YH, et al: Exosomes derived from imatinib-resistant chronic myeloid leukemia cells mediate a horizontal transfer of drug-resistant trait by delivering miR-365. Exp Cell Res. 362:386–393. 2018.PubMed/NCBI View Article : Google Scholar


Liu Y, Song B, Wei Y, Chen F, Chi Y, Fan H, Liu N, Li Z, Han Z and Ma F: Exosomes from mesenchymal stromal cells enhance imatinib-induced apoptosis in human leukemia cells via activation of caspase signaling pathway. Cytotherapy. 20:181–188. 2018.PubMed/NCBI View Article : Google Scholar


Yu D, Li Y, Wang M, Gu J, Xu W, Cai H, Fang X and Zhang X: Exosomes as a new frontier of cancer liquid biopsy. Mol Cancer. 21(56)2022.PubMed/NCBI View Article : Google Scholar


Jia Y, Chen Y, Wang Q, Jayasinghe U, Luo X, Wei Q, Wang J, Xiong H, Chen C, Xu B, et al: Exosome: Emerging biomarker in breast cancer. Oncotarget. 8:41717–41733. 2017.PubMed/NCBI View Article : Google Scholar


Boyiadzis M and Whiteside TL: Plasma-derived exosomes in acute myeloid leukemia for detection of minimal residual disease: Are we ready? Expert Rev Mol Diagn. 16:623–629. 2016.PubMed/NCBI View Article : Google Scholar


An T, Qin S, Xu Y, Tang Y, Huang Y, Situ B, Inal JM and Zheng L: Exosomes serve as tumour markers for personalized diagnostics owing to their important role in cancer metastasis. J Extracell Vesicles. 4(27522)2015.PubMed/NCBI View Article : Google Scholar


Bobrie A, Colombo M, Raposo G and Théry C: Exosome secretion: Molecular mechanisms and roles in immune responses. Traffic. 12:1659–1668. 2011.PubMed/NCBI View Article : Google Scholar


Tzoran I, Rebibo-Sabbah A, Brenner B and Aharon A: Disease dynamics in patients with acute myeloid leukemia: New biomarkers. Exp Hematol. 43:936–943. 2015.PubMed/NCBI View Article : Google Scholar


Hornick NI, Huan J, Doron B, Goloviznina NA, Lapidus J, Chang BH and Kurre P: Serum exosome MicroRNA as a minimally-invasive early biomarker of AML. Sci Rep. 5(11295)2015.PubMed/NCBI View Article : Google Scholar


Hong CS, Muller L, Whiteside TL and Boyiadzis M: Plasma exosomes as markers of therapeutic response in patients with acute myeloid leukemia. Front Immunol. 5(160)2014.PubMed/NCBI View Article : Google Scholar


Li Q, Wu Y, Zhang Y, Sun H, Lu Z, Du K, Fang S and Li W: miR-125b regulates cell progression in chronic myeloid leukemia via targeting BAK1. Am J Transl Res. 8:447–459. 2016.PubMed/NCBI


Jiang L, Deng T, Wang D and Xiao Y: Elevated serum exosomal miR-125b level as a potential marker for poor prognosis in intermediate-risk acute myeloid leukemia. Acta Haematol. 140:183–192. 2018.PubMed/NCBI View Article : Google Scholar


Lin X, Ling Q, Lv Y, Ye W, Huang J, Li X, Guo Q, Wang J, Li Z and Jin J: Plasma exosome-derived microRNA-532 as a novel predictor for acute myeloid leukemia. Cancer Biomark. 28:151–158. 2020.PubMed/NCBI View Article : Google Scholar


Ferrajoli A, Shanafelt TD, Ivan C, Shimizu M, Rabe KG, Nouraee N, Ikuo M, Ghosh AK, Lerner S, Rassenti LZ, et al: Prognostic value of miR-155 in individuals with monoclonal B-cell lymphocytosis and patients with B chronic lymphocytic leukemia. Blood. 122:1891–1899. 2013.PubMed/NCBI View Article : Google Scholar


Stamatopoulos B, Van Damme M, Crompot E, Dessars B, Housni HE, Mineur P, Meuleman N, Bron D and Lagneaux L: Opposite prognostic significance of cellular and serum circulating MicroRNA-150 in patients with chronic lymphocytic leukemia. Mol Med. 21:123–133. 2015.PubMed/NCBI View Article : Google Scholar


Okimoto RA and Van Etten RA: Navigating the road toward optimal initial therapy for chronic myeloid leukemia. Curr Opin Hematol. 18:89–97. 2011.PubMed/NCBI View Article : Google Scholar


Jabbour E and Kantarjian H: Chronic myeloid leukemia: 2020 Update on diagnosis, therapy and monitoring. Am J Hematol. 95:691–709. 2020.PubMed/NCBI View Article : Google Scholar


Bernardi S, Foroni C, Zanaglio C, Re F, Polverelli N, Turra A, Morello E, Farina M, Cattina F, Gandolfi L, et al: Feasibility of tumor-derived exosome enrichment in the onco-hematology leukemic model of chronic myeloid leukemia. Int J Mol Med. 44:2133–2144. 2019.PubMed/NCBI View Article : Google Scholar


Kibria G, Ramos EK, Wan Y, Gius DR and Liu H: Exosomes as a drug delivery system in cancer therapy: Potential and challenges. Mol Pharm. 15:3625–3633. 2018.PubMed/NCBI View Article : Google Scholar


Ha D, Yang N and Nadithe V: Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: Current perspectives and future challenges. Acta Pharm Sin B. 6:287–296. 2016.PubMed/NCBI View Article : Google Scholar


Bellavia D, Raimondo S, Calabrese G, Forte S, Cristaldi M, Patinella A, Memeo L, Manno M, Raccosta S, Diana P, et al: Interleukin 3-receptor targeted exosomes inhibit in vitro and in vivo chronic myelogenous leukemia cell growth. Theranostics. 7:1333–1345. 2017.PubMed/NCBI View Article : Google Scholar


Taverna S, Giallombardo M, Pucci M, Flugy A, Manno M, Raccosta S, Rolfo C, De Leo G and Alessandro R: Curcumin inhibits in vitro and in vivo chronic myelogenous leukemia cells growth: A possible role for exosomal disposal of miR-21. Oncotarget. 6:21918–21933. 2015.PubMed/NCBI View Article : Google Scholar


Gu X, Erb U, Büchler MW and Zöller M: Improved vaccine efficacy of tumor exosome compared to tumor lysate loaded dendritic cells in mice. Int J Cancer. 136:E74–E84. 2015.PubMed/NCBI View Article : Google Scholar


Cheng Q, Shi X and Zhang Y: Reprogramming exosomes for immunotherapy. Methods Mol Biol. 2097:197–209. 2020.PubMed/NCBI View Article : Google Scholar


Qiao L, Hu S, Huang K, Su T, Li Z, Vandergriff A, Cores J, Dinh PU, Allen T, Shen D, et al: Tumor cell-derived exosomes home to their cells of origin and can be used as Trojan horses to deliver cancer drugs. Theranostics. 10:3474–3487. 2020.PubMed/NCBI View Article : Google Scholar

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Chen L, Xie T, Wei B and Di D: Tumour‑derived exosomes and their emerging roles in leukaemia (Review). Exp Ther Med 25: 126, 2023
Chen, L., Xie, T., Wei, B., & Di, D. (2023). Tumour‑derived exosomes and their emerging roles in leukaemia (Review). Experimental and Therapeutic Medicine, 25, 126.
Chen, L., Xie, T., Wei, B., Di, D."Tumour‑derived exosomes and their emerging roles in leukaemia (Review)". Experimental and Therapeutic Medicine 25.3 (2023): 126.
Chen, L., Xie, T., Wei, B., Di, D."Tumour‑derived exosomes and their emerging roles in leukaemia (Review)". Experimental and Therapeutic Medicine 25, no. 3 (2023): 126.