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
August-2022 Volume 48 Issue 2

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
August-2022 Volume 48 Issue 2

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

  • Supplementary Files
    • Supplementary_Data1.pdf
    • Supplementary_Data2.pdf
Article Open Access

Genome‑wide expression and methylation analyses reveal aberrant cell adhesion signaling in tyrosine kinase inhibitor‑resistant CML cells

  • Authors:
    • Meike Kaehler
    • Merit Litterst
    • Julia Kolarova
    • Ruwen Böhm
    • Henrike Bruckmueller
    • Ole Ammerpohl
    • Ingolf Cascorbi
    • Inga Nagel
  • View Affiliations / Copyright

    Affiliations: Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig‑Holstein, Campus Kiel, D-24105 Kiel, Germany, Institute of Human Genetics, Ulm University and Ulm Medical Center, D-89081 Ulm, Germany
    Copyright: © Kaehler et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 144
    |
    Published online on: June 22, 2022
       https://doi.org/10.3892/or.2022.8355
  • 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

Although chronic myeloid leukemia (CML) can be effectively treated using BCR‑ABL1 kinase inhibitors, resistance due to kinase alterations or to BCR‑ABL1 independent mechanisms remain a therapeutic challenge. For the latter, the underlying mechanisms are widely discussed; for instance, gene expression changes, epigenetic factors and alternative signaling pathway activation. In the present study, in vitro‑CML cell models of resistance against the tyrosine kinase inhibitors (TKIs) imatinib (0.5 and 2 µM) and nilotinib (0.1 µM) with biological replicates were generated to identify novel mechanisms of resistance. Subsequently, genome‑wide mRNA expression and DNA methylation were analyzed. While mRNA expression patterns differed largely between biological replicates, there was an overlap of 71 genes differentially expressed between cells resistant against imatinib or nilotinib. Moreover, all TKI resistant cell lines demonstrated a slight hypermethylation compared with native cells. In a combined analysis of 151 genes differentially expressed in the biological replicates of imatinib resistance, cell adhesion signaling, in particular the cellular matrix protein fibronectin 1 (FN1), was significantly dysregulated. This gene was also downregulated in nilotinib resistance. Further analyses showed significant FN1‑downregulation in imatinib resistance on mRNA (P<0.001) and protein level (P<0.001). SiRNA‑mediated FN1‑knockdown in native cells reduced cell adhesion (P=0.02), decreased imatinib susceptibility visible by higher Ki‑67 expression (1.5‑fold, P=0.04) and increased cell number (1.5‑fold, P=0.03). Vice versa, recovery of FN1‑expression in imatinib resistant cells was sufficient to partially restore the response to imatinib. Overall, these results suggested a role of cell adhesion signaling and fibronectin 1 in TKI resistant CML and a potential target for novel strategies in treatment of resistant CML.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Deininger MW, Goldman JM and Melo JV: The molecular biology of chronic myeloid leukemia. Blood. 96:3343–3356. 2000. View Article : Google Scholar : PubMed/NCBI

2 

Quintas-Cardama A and Cortes J: Molecular biology of bcr-abl1-positive chronic myeloid leukemia. Blood. 113:1619–1630. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, Zimmermann J and Lydon NB: Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med. 2:561–566. 1996. View Article : Google Scholar : PubMed/NCBI

4 

Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, Cervantes F, Clark RE, Cortes JE, Guilhot F, et al: European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 122:872–884. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Hochhaus A, Larson RA, Guilhot F, Radich JP, Branford S, Hughes TP, Baccarani M, Deininger MW, Cervantes F, Fujihara S, et al: Long-term outcomes of imatinib treatment for chronic myeloid leukemia. N Engl J Med. 376:917–927. 2017. View Article : Google Scholar : PubMed/NCBI

6 

Milojkovic D and Apperley J: Mechanisms of resistance to imatinib and second-generation tyrosine inhibitors in chronic myeloid leukemia. Clin Cancer Res. 15:7519–7527. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Soverini S, De Benedittis C, Papayannidis C, Paolini S, Venturi C, Iacobucci I, Luppi M, Bresciani P, Salvucci M, Russo D, et al: Drug resistance and BCR-ABL kinase domain mutations in Philadelphia chromosome-positive acute lymphoblastic leukemia from the imatinib to the second-generation tyrosine kinase inhibitor era: The main changes are in the type of mutations, but not in the frequency of mutation involvement. Cancer. 120:1002–1009. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Zabriskie MS, Eide CA, Tantravahi SK, Vellore NA, Estrada J, Nicolini FE, Khoury HJ, Larson RA, Konopleva M, Cortes JE, et al: BCR-ABL1 compound mutations combining key kinase domain positions confer clinical resistance to ponatinib in Ph chromosome-positive leukemia. Cancer Cell. 26:428–442. 2014. View Article : Google Scholar : PubMed/NCBI

9 

de Lavallade H and Kizilors A: The importance of mutational analyses in chronic myeloid leukaemia for treatment choice. Eur Med J Oncol. 4:86–95. 2016.

10 

Jelinek J, Gharibyan V, Estecio MR, Kondo K, He R, Chung W, Lu Y, Zhang N, Liang S, Kantarjian HM, et al: Aberrant DNA methylation is associated with disease progression, resistance to imatinib and shortened survival in chronic myelogenous leukemia. PLoS One. 6:e221102011. View Article : Google Scholar : PubMed/NCBI

11 

Turrini E, Haenisch S, Laechelt S, Diewock T, Bruhn O and Cascorbi I: MicroRNA profiling in K-562 cells under imatinib treatment: Influence of miR-212 and miR-328 on ABCG2 expression. Pharmacogenet Genomics. 22:198–205. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Liu Y, Song Y, Ma W, Zheng W and Yin H: Decreased microRNA-30a levels are associated with enhanced ABL1 and BCR-ABL1 expression in chronic myeloid leukemia. Leuk Res. 37:349–356. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Shibuta T, Honda E, Shiotsu H, Tanaka Y, Vellasamy S, Shiratsuchi M and Umemura T: Imatinib induces demethylation of miR-203 gene: An epigenetic mechanism of anti-tumor effect of imatinib. Leuk Res. 37:1278–1286. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Cortes J and O'Dwyer ME: Clonal evolution in chronic myelogenous leukemia. Hematol Oncol Clin North Am. 18:671–684. 2004. View Article : Google Scholar : PubMed/NCBI

15 

Corbin AS, Agarwal A, Loriaux M, Cortes J, Deininger MW and Druker BJ: Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity. J Clin Invest. 121:396–409. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Hamad A, Sahli Z, El Sabban M, Mouteirik M and Nasr R: Emerging therapeutic strategies for targeting chronic myeloid leukemia stem cells. Stem Cells Int. 2013:7243602013. View Article : Google Scholar : PubMed/NCBI

17 

Kaehler M, Ruemenapp J, Gonnermann D, Nagel I, Bruhn O, Haenisch S, Ammerpohl O, Wesch D, Cascorbi I and Bruckmueller H: MicroRNA-212/ABCG2-axis contributes to development of imatinib-resistance in leukemic cells. Oncotarget. 8:92018–92031. 2017. View Article : Google Scholar : PubMed/NCBI

18 

Oliveros JC: An interactive tool for comparing lists with Venn's diagrams. 2007-2015.https://bioinfogp.cnb.csic.es/tools/venny/index.html

19 

Walter W, Sanchez-Cabo F and Ricote M: GOplot: An R package for visually combining expression data with functional analysis. Bioinformatics. 31:2912–2914. 2015. View Article : Google Scholar : PubMed/NCBI

20 

RStudio Team (2020), . RStudio: Integrated Development for R. RStudio. PBC; Boston, MA: http://www.rstudio.com/

21 

Pedregosa F, Varoquaux G, Gramfort A, Michel V and Thirion B: Scikit-learn: Machine learning in python. J Machine Learning Research. 12:2825–2830. 2011.

22 

Kaehler M, Dworschak M, Rodin JP, Ruemenapp J, Vater I, Penas EMM, Liu C, Cascorbi I and Nagel I: Zfp36l1 plays an ambiguous role in the regulation of cell expansion and negatively regulates Cdkn1a in chronic myeloid leukemia cells. Exp Hematol. 99:54–64. 2021. View Article : Google Scholar : PubMed/NCBI

23 

Waetzig V, Haeusgen W, Andres C, Frehse S, Reinecke K, Bruckmueller H, Ruwen Boehm H, Herdegen T and Cascorbi I: Retinoic acid-induced survival effects in SH-SY5Y neuroblastoma cells. J Cell Biochem. 120:5974–5986. 2019. View Article : Google Scholar : PubMed/NCBI

24 

Bruhn O, Lindsay M, Wiebel F, Kaehler M, Nagel I, Böhm R, Röder C and Cascorbi I: Alternative polyadenylation of ABC transporters of the C-family (ABCC1, ABCC2, ABCC3) and implications on posttranscriptional Micro-RNA regulation. Mol Pharmacol. 97:112–122. 2020. View Article : Google Scholar : PubMed/NCBI

25 

Edeki C: Comparative study of microarray and next generation sequencing technologies. IJCSMC. 1:15–20. 2012.

26 

Pop L, Zanoaga O, Chiroi P, Nutu A, Korban SS, Stefan C, Irimie A and Berindan-Neagoe I: Microarrays and NGS for drug discovery. Drug Design. Parikesit AA: IntechOpen; 2021

27 

Bakay M, Chen YW, Borup R, Zhao P, Nagaraju K and Hoffman EP: Sources of variability and effect of experimental approach on expression profiling data interpretation. BMC Bioinformatics. 3:42002. View Article : Google Scholar : PubMed/NCBI

28 

Bammler T, Beyer RP, Bhattacharya S, Boorman GA, Boyles A, Bradford BU, Bumgarner RE, Bushel PR, Chaturvedi K, Choi D, et al: Standardizing global gene expression analysis between laboratories and across platforms. Nat Methods. 2:351–356. 2005. View Article : Google Scholar : PubMed/NCBI

29 

Draghici S, Khatri P, Eklund AC and Szallasi Z: Reliability and reproducibility issues in DNA microarray measurements. Trends Genet. 22:101–109. 2006. View Article : Google Scholar : PubMed/NCBI

30 

Chung YJ, Kim TM, Kim DW, Namkoong H, Kim HK, Ha SA, Kim S, Shin SM, Kim JH, Lee YJ, et al: Gene expression signatures associated with the resistance to imatinib. Leukemia. 20:1542–1550. 2006. View Article : Google Scholar : PubMed/NCBI

31 

Kim TM, Ha SA, Kim HK, Yoo J, Kim S, Yim SH, Jung SH, Kim DW, Chung YJ and Kim JW: Gene expression signatures associated with the in vitro resistance to two tyrosine kinase inhibitors nilotinib and imatinib. Blood Cancer J. 1:e322011. View Article : Google Scholar : PubMed/NCBI

32 

Krause DS and Scadden DT: A hostel for the hostile: The bone marrow niche in hematologic neoplasms. Haematologica. 100:1376–1387. 2015. View Article : Google Scholar : PubMed/NCBI

33 

Bazzoni G, Carlesso N, Griffin JD and Hemler ME: Bcr/Abl expression stimulates integrin function in hematopoietic cell lines. J Clin Invest. 98:521–528. 1996. View Article : Google Scholar : PubMed/NCBI

34 

Nishihara T, Miura Y, Tohyama Y, Mizutani C, Hishita T, Ichiyama S, Uchiyama T and Tohyama K: Effects of the tyrosine kinase inhibitor imatinib mesylate on a Bcr-Abl-positive cell line: Suppression of autonomous cell growth but no effect on decreased adhesive property and morphological changes. Int J Hematol. 78:233–240. 2003. View Article : Google Scholar : PubMed/NCBI

35 

Li Y, Clough N, Sun X, Yu W, Abbott BL, Hogan CJ and Dai Z: Bcr-Abl induces abnormal cytoskeleton remodeling, beta1 integrin clustering and increased cell adhesion to fibronectin through the Abl interactor 1 pathway. J Cell Sci. 120:1436–1446. 2007. View Article : Google Scholar : PubMed/NCBI

36 

Windisch R, Pirschtat N, Kellner C, Chen-Wichmann L, Lausen J, Humpe A, Krause DS and Wichmann C: Oncogenic deregulation of cell adhesion molecules in leukemia. Cancers (Basel). 11:3112019. View Article : Google Scholar : PubMed/NCBI

37 

Damiano JS, Hazlehurst LA and Dalton WS: Cell adhesion-mediated drug resistance (CAM-DR) protects the K562 chronic myelogenous leukemia cell line from apoptosis induced by BCR/ABL inhibition cytotoxic drugs and gamma-irradiation. Leukemia. 15:1232–1239. 2001. View Article : Google Scholar : PubMed/NCBI

38 

Obr A, Roselova P, Grebenova D and Kuželová K: Real-time analysis of imatinib- and dasatinib-induced effects on chronic myelogenous leukemia cell interaction with fibronectin. PLoS One. 9:e1073672014. View Article : Google Scholar : PubMed/NCBI

39 

Kumar R, Pereira RS, Zanetti C, Minciacchi VR, Merten M, Meister M, Niemann J, Dietz MS, Rüssel N, Schnütgen F, et al: Specific targetable interactions with the microenvironment influence imatinib-resistant chronic myeloid leukemia. Leukemia. 34:2087–2101. 2020. View Article : Google Scholar : PubMed/NCBI

40 

Wlodek J and Pituch-Noworolska A: The influence of fibronectin on proliferation and apoptosis of acute lymphoblastic leukaemia cells in vitro. Pol J Pathol. 69:62–66. 2018. View Article : Google Scholar : PubMed/NCBI

41 

Baharudin R, Ab Mutalib NS, Othman SN, Sagap I, Rose IM, Mokhtar NM and Jamal R: Identification of predictive DNA methylation biomarkers for chemotherapy response in colorectal cancer. Front Pharmacol. 8:472017. View Article : Google Scholar : PubMed/NCBI

42 

Guo R, Wu G, Li H, Qian P, Han J, Pan F, Li W, Li J and Ji F: Promoter methylation profiles between human lung adenocarcinoma multidrug resistant A549/cisplatin (A549/DDP) cells and its progenitor A549 cells. Biol Pharm Bull. 36:1310–1316. 2013. View Article : Google Scholar : PubMed/NCBI

43 

Romero-Garcia S, Prado-Garcia H and Carlos-Reyes A: Role of DNA methylation in the resistance to therapy in solid tumors. Front Oncol. 10:11522020. View Article : Google Scholar : PubMed/NCBI

44 

Lebecque B, Bourgne C, Vidal V and Berger MG: DNA methylation and intra-clonal heterogeneity: The chronic myeloid leukemia model. Cancers (Basel). 13:35872021. View Article : Google Scholar : PubMed/NCBI

45 

Amabile G, Di Ruscio A, Müller F, Welner RS, Yang H, Ebralidze AK, Zhang H, Levantini E, Qi L, Martinelli G, et al: Dissecting the role of aberrant DNA methylation in human leukaemia. Nat Commun. 6:70912015. View Article : Google Scholar : PubMed/NCBI

46 

Jose-Eneriz ES, Agirre X, Jimenez-Velasco A, Cordeu L, Martín V, Arqueros V, Gárate L, Fresquet V, Cervantes F, Martínez-Climent JA, et al: Epigenetic down-regulation of BIM expression is associated with reduced optimal responses to imatinib treatment in chronic myeloid leukaemia. Eur J Cancer. 45:1877–1889. 2009. View Article : Google Scholar : PubMed/NCBI

47 

Elias MH, Baba AA, Husin A, Sulong S, Hassan R, Sim GA, Wahid SFA and Ankathil R: HOXA4 gene promoter hypermethylation as an epigenetic mechanism mediating resistance to imatinib mesylate in chronic myeloid leukemia patients. Biomed Res Int. 2013:1297152013. View Article : Google Scholar : PubMed/NCBI

48 

Nishioka C, Ikezoe T, Yang J, Udaka K and Yokoyama A: Imatinib causes epigenetic alterations of PTEN gene via upregulation of DNA methyltransferases and polycomb group proteins. Blood Cancer J. 1:e482011. View Article : Google Scholar : PubMed/NCBI

49 

Borisov N, Tkachev V, Suntsova M, Kovalchuk O, Zhavoronkov A, Muchnik I and Buzdin A: A method of gene expression data transfer from cell lines to cancer patients for machine-learning prediction of drug efficiency. Cell Cycle. 17:486–491. 2018. View Article : Google Scholar : PubMed/NCBI

50 

Mirabelli P, Coppola L and Salvatore M: Cancer cell lines are useful model systems for medical research. Cancers. 11:10982019. View Article : Google Scholar : PubMed/NCBI

51 

Rumjanek VM, Vidal RS and Maia RC: Multidrug resistance in chronic myeloid leukaemia: How much can we learn from MDR-CML cell lines? Biosci Rep. 33:e000812013. View Article : Google Scholar : PubMed/NCBI

52 

McDermott M, Eustace AJ, Busschots S, Breen L, Crown J, Clynes M, O'Donovan N and Stordal B: In vitro development of chemotherapy and targeted therapy drug-resistant cancer cell lines: A practical guide with case studies. Front Oncol. 4:402014. View Article : Google Scholar : PubMed/NCBI

53 

Peng B, Lloyd P and Schran H: Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 44:879–894. 2005. View Article : Google Scholar : PubMed/NCBI

54 

de Kogel CE and Schellens JH: Imatinib. Oncologist. 12:1390–1394. 2007. View Article : Google Scholar : PubMed/NCBI

55 

Picard S, Titier K, Etienne G, Teilhet E, Ducint D, Bernard MA, Lassalle R, Marit G, Reiffers J, Begaud B, et al: Trough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia. Blood. 109:3496–3499. 2007. View Article : Google Scholar : PubMed/NCBI

56 

Gromicho M, Dinis J, Magalhães M, Fernandes AR, Tavares P, Laires A, Rueff J and Rodrigues AS: Development of imatinib and dasatinib resistance: dynamics of expression of drug transporters ABCB1, ABCC1, ABCG2, MVP, and SLC22A1. Leuk Lymphoma. 52:1980–1990. 2011. View Article : Google Scholar : PubMed/NCBI

57 

Eadie LN, Hughes TP and White DL: ABCB1 overexpression is a key initiator of resistance to tyrosine kinase inhibitors in CML cell lines. PLoS One. 11:e01614702016. View Article : Google Scholar : PubMed/NCBI

58 

de Lima LT, Vivona D, Bueno CT, Hirata RDC, Hirata MH, Luchessi AD, de Castro FA, de Lourdes F, Chauffaille M, Zanichelli MA, Chiattone CS, et al: Reduced ABCG2 and increased SLC22A1 mRNA expression are associated with imatinib response in chronic myeloid leukemia. Med Oncol. 31:8512014. View Article : Google Scholar : PubMed/NCBI

59 

Nies AT, Schaeffeler E, van der Kuip H, Cascorbi I, Bruhn O, Kneba M, Pott C, Hofmann U, Volk C, Hu S, et al: Cellular uptake of imatinib into leukemic cells is independent of human organic cation transporter 1 (OCT1). Clin Cancer Res. 20:985–994. 2014. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Kaehler M, Litterst M, Kolarova J, Böhm R, Bruckmueller H, Ammerpohl O, Cascorbi I and Nagel I: Genome‑wide expression and methylation analyses reveal aberrant cell adhesion signaling in tyrosine kinase inhibitor‑resistant CML cells. Oncol Rep 48: 144, 2022.
APA
Kaehler, M., Litterst, M., Kolarova, J., Böhm, R., Bruckmueller, H., Ammerpohl, O. ... Nagel, I. (2022). Genome‑wide expression and methylation analyses reveal aberrant cell adhesion signaling in tyrosine kinase inhibitor‑resistant CML cells. Oncology Reports, 48, 144. https://doi.org/10.3892/or.2022.8355
MLA
Kaehler, M., Litterst, M., Kolarova, J., Böhm, R., Bruckmueller, H., Ammerpohl, O., Cascorbi, I., Nagel, I."Genome‑wide expression and methylation analyses reveal aberrant cell adhesion signaling in tyrosine kinase inhibitor‑resistant CML cells". Oncology Reports 48.2 (2022): 144.
Chicago
Kaehler, M., Litterst, M., Kolarova, J., Böhm, R., Bruckmueller, H., Ammerpohl, O., Cascorbi, I., Nagel, I."Genome‑wide expression and methylation analyses reveal aberrant cell adhesion signaling in tyrosine kinase inhibitor‑resistant CML cells". Oncology Reports 48, no. 2 (2022): 144. https://doi.org/10.3892/or.2022.8355
Copy and paste a formatted citation
x
Spandidos Publications style
Kaehler M, Litterst M, Kolarova J, Böhm R, Bruckmueller H, Ammerpohl O, Cascorbi I and Nagel I: Genome‑wide expression and methylation analyses reveal aberrant cell adhesion signaling in tyrosine kinase inhibitor‑resistant CML cells. Oncol Rep 48: 144, 2022.
APA
Kaehler, M., Litterst, M., Kolarova, J., Böhm, R., Bruckmueller, H., Ammerpohl, O. ... Nagel, I. (2022). Genome‑wide expression and methylation analyses reveal aberrant cell adhesion signaling in tyrosine kinase inhibitor‑resistant CML cells. Oncology Reports, 48, 144. https://doi.org/10.3892/or.2022.8355
MLA
Kaehler, M., Litterst, M., Kolarova, J., Böhm, R., Bruckmueller, H., Ammerpohl, O., Cascorbi, I., Nagel, I."Genome‑wide expression and methylation analyses reveal aberrant cell adhesion signaling in tyrosine kinase inhibitor‑resistant CML cells". Oncology Reports 48.2 (2022): 144.
Chicago
Kaehler, M., Litterst, M., Kolarova, J., Böhm, R., Bruckmueller, H., Ammerpohl, O., Cascorbi, I., Nagel, I."Genome‑wide expression and methylation analyses reveal aberrant cell adhesion signaling in tyrosine kinase inhibitor‑resistant CML cells". Oncology Reports 48, no. 2 (2022): 144. https://doi.org/10.3892/or.2022.8355
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