Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
September-2016 Volume 36 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
September-2016 Volume 36 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Amyloid precursor protein cooperates with c-KIT mutation/overexpression to regulate cell apoptosis in AML1-ETO-positive leukemia via the PI3K/AKT signaling pathway

  • Authors:
    • Guopan Yu
    • Changxin Yin
    • Ling Jiang
    • Zhongxin Zheng
    • Zhixiang Wang
    • Chunli Wang
    • Hongsheng Zhou
    • Xuejie Jiang
    • Qifa Liu
    • Fanyi Meng
  • View Affiliations / Copyright

    Affiliations: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
  • Pages: 1626-1632
    |
    Published online on: July 21, 2016
       https://doi.org/10.3892/or.2016.4963
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

It has been reported that amyloid precursor protein (APP) promotes cell proliferation and metastasis in various types of solid cancers. In our previous study, we showed that APP is highly expressed and regulates leukemia cell migration in AML1‑ETO-positive (AE) leukemia. Whether APP is involved in the regulation of AE leukemia cell proliferation or apoptosis is unclear. In the present study we focused on the correlation of APP with c-KIT mutation/overexpression and cell proliferation and apoptosis in AE leukemia. APP and c-KIT expression detected by quantitative real-time (qPCR) method, and c-KIT mutations screened using PCR in bone marrow cells from 65 patients with AE leukemia before their first chemotherapy, were simultaneously assessed. Furthermore, the Kasumi-1 cell line was chosen as the cell model, and the APP gene was knocked down using siRNA technology. The correlation of cell cycle distribution and apoptosis and c-Kit expression with APP expression levels, as well as the regulation of the PI3K/AKT signaling pathway by APP were analyzed in the Kasumi-1 cell line. The results showed that peripheral white blood cell counts (P=0.008) and bone marrow cellularity (P=0.031), but not bone marrow blasts, were correlated with APP expression. Moreover, the patients with APP high expression had a significantly higher incidence of c-KIT mutations (P<0.001) and increased levels of c-KIT expression (P=0.001) and poorer disease outcome. In the Kasumi-1 cell line, as compared with the wild-type and negative control cells, cell apoptosis, both early (P<0.001) and late (P<0.001), was significantly increased when the APP gene was knocked down, concomitant with reduced levels of anti-apoptotic protein Bcl-2 and increased levels of caspase-3 and -9, however, no apparent change was observed in the cell cycle distribution (P>0.05). Moreover, the knockdown of APP markedly decreased c-KIT expression at both the transcription (as evidenced by qPCR analysis) and translation (as confirmed by CD117 assay and western blot analysis) levels, as well as p-AKT and its downstream targets including NF-κB, p53 and Bcl-2. In conclusion, APP may cooperate with c-KIT mutation/overexpression in the regulation of cell apoptosis but not proliferation in AE leukemia via the PI3K/AKT signaling pathway.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Rowley JD: Identificaton of a translocation with quinacrine fluorescence in a patient with acute leukemia. Ann Genet. 16:109–112. 1973.PubMed/NCBI

2 

Yergeau DA, Hetherington CJ, Wang Q, Zhang P, Sharpe AH, Binder M, Marín-Padilla M, Tenen DG, Speck NA and Zhang DE: Embryonic lethality and impairment of haematopoiesis in mice heterozygous for an AML1-ETO fusion gene. Nat Genet. 15:303–306. 1997. View Article : Google Scholar : PubMed/NCBI

3 

Higuchi M, O'Brien D, Kumaravelu P, Lenny N, Yeoh EJ and Downing JR: Expression of a conditional AML1-ETO oncogene bypasses embryonic lethality and establishes a murine model of human t(8;21) acute myeloid leukemia. Cancer Cell. 1:63–74. 2002. View Article : Google Scholar : PubMed/NCBI

4 

Rhoades KL, Hetherington CJ, Harakawa N, Yergeau DA, Zhou L, Liu LQ, Little MT, Tenen DG and Zhang DE and Zhang DE: Analysis of the role of AML1-ETO in leukemogenesis, using an inducible transgenic mouse model. Blood. 96:2108–2115. 2000.PubMed/NCBI

5 

Jiao B, Wu CF, Liang Y, Chen HM, Xiong SM, Chen B, Shi JY, Wang YY, Wang JH, Chen Y, et al: AML1-ETO9a is correlated with C-KIT overexpression/mutations and indicates poor disease outcome in t(8;21) acute myeloid leukemia-M2. Leukemia. 23:1598–1604. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Paschka P, Marcucci G, Ruppert AS, Mrózek K, Chen H, Kittles RA, Vukosavljevic T, Perrotti D, Vardiman JW, Carroll AJ, et al Cancer and Leukemia Group B: Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv(16) and t(8;21): A Cancer and Leukemia Group B Study. J Clin Oncol. 24:3904–3911. 2006. View Article : Google Scholar : PubMed/NCBI

7 

Schnittger S, Kohl TM, Haferlach T, Kern W, Hiddemann W, Spiekermann K and Schoch C: KIT-D816 mutations in AML1-ETO-positive AML are associated with impaired event-free and overall survival. Blood. 107:1791–1799. 2006. View Article : Google Scholar

8 

Wang YY, Zhao LJ, Wu CF, Liu P, Shi L, Liang Y, Xiong SM, Mi JQ, Chen Z, Ren R, et al: C-KIT mutation cooperates with full-length AML1-ETO to induce acute myeloid leukemia in mice. Proc Natl Acad Sci USA. 108:2450–2455. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Nick HJ, Kim HG, Chang CW, Harris KW, Reddy V and Klug CA: Distinct classes of c-Kit-activating mutations differ in their ability to promote RUNX1-ETO-associated acute myeloid leukemia. Blood. 119:1522–1531. 2012. View Article : Google Scholar :

10 

Wichmann C, Quagliano-Lo Coco I, Yildiz Ö, Chen-Wichmann L, Weber H, Syzonenko T, Döring C, Brendel C, Ponnusamy K, Kinner A, et al: Activating c-KIT mutations confer oncogenic cooperativity and rescue RUNX1/ETO-induced DNA damage and apoptosis in human primary CD34+ hematopoietic progenitors. Leukemia. 29:279–289. 2015. View Article : Google Scholar

11 

Zhang MY, Zheng CY, Zou MM, Zhu JW, Zhang Y, Wang J, Liu CF, Li QF, Xiao ZC, Li S, et al: Lamotrigine attenuates deficits in synaptic plasticity and accumulation of amyloid plaques in APP/PS1 transgenic mice. Neurobiol Aging. 35:2713–2725. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Hansel DE, Rahman A, Wehner S, Herzog V, Yeo CJ and Maitra A: Increased expression and processing of the Alzheimer amyloid precursor protein in pancreatic cancer may influence cellular proliferation. Cancer Res. 63:7032–7037. 2003.PubMed/NCBI

13 

Ko SY, Lin SC, Chang KW, Wong YK, Liu CJ, Chi CW and Liu TY: Increased expression of amyloid precursor protein in oral squamous cell carcinoma. Int J Cancer. 111:727–732. 2004. View Article : Google Scholar : PubMed/NCBI

14 

Krause K, Karger S, Sheu SY, Aigner T, Kursawe R, Gimm O, Schmid KW, Dralle H and Fuhrer D: Evidence for a role of the amyloid precursor protein in thyroid carcinogenesis. J Endocrinol. 198:291–299. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Takayama K, Tsutsumi S, Suzuki T, Horie-Inoue K, Ikeda K, Kaneshiro K, Fujimura T, Kumagai J, Urano T, Sakaki Y, et al: Amyloid precursor protein is a primary androgen target gene that promotes prostate cancer growth. Cancer Res. 69:137–142. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Baldus CD, Liyanarachchi S, Mrózek K, Auer H, Tanner SM, Guimond M, Ruppert AS, Mohamed N, Davuluri RV, Caligiuri MA, et al: Acute myeloid leukemia with complex karyotypes and abnormal chromosome 21: Amplification discloses overexpression of APP, ETS2, and ERG genes. Proc Natl Acad Sci USA. 101:3915–3920. 2004. View Article : Google Scholar : PubMed/NCBI

17 

Wang W, Meng FY, Huang ZF, Huang M and Liu LX: Expression and role of amyloid precrusor protein gene in acute myeloid leukemia. Chin J Hematol. 31:309–314. 2010.In Chinese.

18 

Jiang L, Yu G, Meng W, Wang Z, Meng F and Ma W: Overexpression of amyloid precursor protein in acute myeloid leukemia enhances extramedullary infiltration by MMP-2. Tumour Biol. 34:629–636. 2013. View Article : Google Scholar

19 

Larizza L, Magnani I and Beghini A: The Kasumi-1 cell line: A t(8;21)-kit mutant model for acute myeloid leukemia. Leuk Lymphoma. 46:247–255. 2005. View Article : Google Scholar

20 

Pulikkan JA, Madera D, Xue L, Bradley P, Landrette SF, Kuo YH, Abbas S, Zhu LJ, Valk P and Castilla LH: Thrombopoietin/MPL participates in initiating and maintaining RUNX1-ETO acute myeloid leukemia via PI3K/AKT signaling. Blood. 120:868–879. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Kumar A, Fernandez-Capetillo O and Carrera AC: Nuclear phosphoinositide 3-kinase β controls double-strand break DNA repair. Proc Natl Acad Sci USA. 107:7491–7496. 2010. View Article : Google Scholar

22 

Sheng S, Qiao M and Pardee AB: Metastasis and AKT activation. J Cell Physiol. 218:451–454. 2009. View Article : Google Scholar

23 

Wang L, Zhao WL, Yan JS, Liu P, Sun HP, Zhou GB, Weng ZY, Wu WL, Weng XQ, Sun XJ, et al: Eriocalyxin B induces apoptosis of t(8;21) leukemia cells through NF-κB and MAPK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner. Cell Death Differ. 14:306–317. 2007. View Article : Google Scholar

24 

Krejci O, Wunderlich M, Geiger H, Chou FS, Schleimer D, Jansen M, Andreassen PR and Mulloy JC: p53 signaling in response to increased DNA damage sensitizes AML1-ETO cells to stress-induced death. Blood. 111:2190–2199. 2008. View Article : Google Scholar

25 

McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Montalto G, Cervello M, Nicoletti F, Fagone P, Malaponte G, Mazzarino MC, et al: Mutations and deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades which alter therapy response. Oncotarget. 3:954–987. 2012. View Article : Google Scholar : PubMed/NCBI

26 

Hart JR and Vogt PK: Phosphorylation of AKT: A mutational analysis. Oncotarget. 2:467–476. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y and Greenberg ME: Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell. 91:231–241. 1997. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Yu G, Yin C, Jiang L, Zheng Z, Wang Z, Wang C, Zhou H, Jiang X, Liu Q, Meng F, Meng F, et al: Amyloid precursor protein cooperates with c-KIT mutation/overexpression to regulate cell apoptosis in AML1-ETO-positive leukemia via the PI3K/AKT signaling pathway. Oncol Rep 36: 1626-1632, 2016.
APA
Yu, G., Yin, C., Jiang, L., Zheng, Z., Wang, Z., Wang, C. ... Meng, F. (2016). Amyloid precursor protein cooperates with c-KIT mutation/overexpression to regulate cell apoptosis in AML1-ETO-positive leukemia via the PI3K/AKT signaling pathway. Oncology Reports, 36, 1626-1632. https://doi.org/10.3892/or.2016.4963
MLA
Yu, G., Yin, C., Jiang, L., Zheng, Z., Wang, Z., Wang, C., Zhou, H., Jiang, X., Liu, Q., Meng, F."Amyloid precursor protein cooperates with c-KIT mutation/overexpression to regulate cell apoptosis in AML1-ETO-positive leukemia via the PI3K/AKT signaling pathway". Oncology Reports 36.3 (2016): 1626-1632.
Chicago
Yu, G., Yin, C., Jiang, L., Zheng, Z., Wang, Z., Wang, C., Zhou, H., Jiang, X., Liu, Q., Meng, F."Amyloid precursor protein cooperates with c-KIT mutation/overexpression to regulate cell apoptosis in AML1-ETO-positive leukemia via the PI3K/AKT signaling pathway". Oncology Reports 36, no. 3 (2016): 1626-1632. https://doi.org/10.3892/or.2016.4963
Copy and paste a formatted citation
x
Spandidos Publications style
Yu G, Yin C, Jiang L, Zheng Z, Wang Z, Wang C, Zhou H, Jiang X, Liu Q, Meng F, Meng F, et al: Amyloid precursor protein cooperates with c-KIT mutation/overexpression to regulate cell apoptosis in AML1-ETO-positive leukemia via the PI3K/AKT signaling pathway. Oncol Rep 36: 1626-1632, 2016.
APA
Yu, G., Yin, C., Jiang, L., Zheng, Z., Wang, Z., Wang, C. ... Meng, F. (2016). Amyloid precursor protein cooperates with c-KIT mutation/overexpression to regulate cell apoptosis in AML1-ETO-positive leukemia via the PI3K/AKT signaling pathway. Oncology Reports, 36, 1626-1632. https://doi.org/10.3892/or.2016.4963
MLA
Yu, G., Yin, C., Jiang, L., Zheng, Z., Wang, Z., Wang, C., Zhou, H., Jiang, X., Liu, Q., Meng, F."Amyloid precursor protein cooperates with c-KIT mutation/overexpression to regulate cell apoptosis in AML1-ETO-positive leukemia via the PI3K/AKT signaling pathway". Oncology Reports 36.3 (2016): 1626-1632.
Chicago
Yu, G., Yin, C., Jiang, L., Zheng, Z., Wang, Z., Wang, C., Zhou, H., Jiang, X., Liu, Q., Meng, F."Amyloid precursor protein cooperates with c-KIT mutation/overexpression to regulate cell apoptosis in AML1-ETO-positive leukemia via the PI3K/AKT signaling pathway". Oncology Reports 36, no. 3 (2016): 1626-1632. https://doi.org/10.3892/or.2016.4963
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team