Semi‑random mutagenesis profile of BCR‑ABL during imatinib resistance acquirement in K562 cells

Dong,Yan; Gao,Xiaotong; Zhao,Yingxin; Wei,Mengying; Xu,Lingmin; Yang,Guodong; Liu,Li

doi:10.3892/mmr.2017.7835

Semi‑random mutagenesis profile of BCR‑ABL during imatinib resistance acquirement in K562 cells

Authors:
- Yan Dong
- Xiaotong Gao
- Yingxin Zhao
- Mengying Wei
- Lingmin Xu
- Guodong Yang
- Li Liu
View Affiliations

Affiliations: Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
Published online on: October 19, 2017 https://doi.org/10.3892/mmr.2017.7835
Pages: 9409-9414
Copyright: © Dong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Although imatinib is effective in chronic myeloid leukemia treatment, imatinib resistance due to the T315I mutation and/or other mutations is a challenge to be overcome. However, how DNA mutation occurs, particularly the T315I mutation, remains unclear. In the current study, the mutagenesis of BCR‑ABL was analyzed via focusing on the process of drug resistance, rather than the final results. Clone sequencing of the BCR‑ABL gene and other control genes was applied in two imatinib‑resistant cell models. The results have indicated that imatinib actively and selectively causes sporadic mutations in the BCR‑ABL gene, however not in the control genes. The majority of the mutations of BCR‑ABL were not the clinically observed T315I mutation, suggesting that the T315I mutation may be due to clonal expansion of cells with survival advantages. Taken together, the results of the current study elucidated the mutagenesis process during drug resistance and thus aids in the management of chemotherapy.

View Figures

View References

1	Huang X, Cortes J and Kantarjian H: Estimations of the increasing prevalence and plateau prevalence of chronic myeloid leukemia in the era of tyrosine kinase inhibitors therapy. Cancer. 118:3123–3127. 2012. View Article : Google Scholar : PubMed/NCBI
2	Ma L, Shan Y, Bai R, Xue L, Eide CA, Ou J, Zhu LJ, Hutchinson L, Cerny J, Khoury HJ, et al: A therapeutically targetable mechanism of BCR-ABL-independent imatinib resistance in chronic myeloid leukemia. Sci Transl Med. 6:252ra1212014. View Article : Google Scholar : PubMed/NCBI
3	Hughes TP, Kaeda J, Branford S, Rudzki Z, Hochhaus A, Hensley ML, Gathmann I, Bolton AE, van Hoomissen IC, Goldman JM, et al: Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N Engl J Med. 349:1423–1432. 2003. View Article : Google Scholar : PubMed/NCBI
4	Berman E, Jhanwar S, Hedvat C, Arcila ME, Wahab OA, Levine R, Maloy M, Ma W and Albitar M: Resistance to imatinib in patients with chronic myelogenous leukemia and the splice variant BCR-ABL1 (35INS). Leuk Res. 49:108–112. 2016. View Article : Google Scholar : PubMed/NCBI
5	Tabarestani S and Movafagh A: New developments in chronic myeloid leukemia: Implications for therapy. Iran J Cancer Prev. 9:e39612016.PubMed/NCBI
6	Wang LX, Wang JD, Chen JJ, Long B, Liu LL, Tu XX, Luo Y, Hu Y, Lin DJ, Lu G, et al: Aurora A kinase inhibitor AKI603 induces cellular senescence in chronic myeloid leukemia cells harboring T315I mutation. Sci Rep. 6:355332016. View Article : Google Scholar : PubMed/NCBI
7	Bixby D and Talpaz M: Seeking the causes and solutions to imatinib-resistance in chronic myeloid leukemia. Leukemia. 25:7–22. 2011. View Article : Google Scholar : PubMed/NCBI
8	Gupta P, Kathawala RJ, Wei L, Wang F, Wang X, Druker BJ, Fu LW and Chen ZS: PBA2, a novel inhibitor of imatinib-resistant BCR-ABL T315I mutation in chronic myeloid leukemia. Cancer Lett. 383:220–229. 2016. View Article : Google Scholar : PubMed/NCBI
9	Speijer D: Does constructive neutral evolution play an important role in the origin of cellular complexity? Making sense of the origins and uses of biological complexity. Bioessays. 33:344–349. 2011. View Article : Google Scholar : PubMed/NCBI
10	Song Y, Shi Y, Carland TM, Lian S, Sasaki T, Schork NJ, Head SR, Kishi S and Schimmel P: p53-Dependent DNA damage response sensitive to editing-defective tRNA synthetase in zebrafish. Proc Natl Acad Sci USA. 113:pp. 8460–8465. 2016; View Article : Google Scholar : PubMed/NCBI
11	Burger G: Non-functional genes repaired at the RNA level. C R Biol. 339:289–295. 2016. View Article : Google Scholar : PubMed/NCBI
12	Nowell PC: The clonal evolution of tumor cell populations. Science. 194:23–28. 1976. View Article : Google Scholar : PubMed/NCBI
13	Gerlinger M, Rowan AJ, Horswell S, Math M, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, et al: Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 366:883–892. 2012. View Article : Google Scholar : PubMed/NCBI
14	Schwer B, Wei PC, Chang AN, Kao J, Du Z, Meyers RM and Alt FW: Transcription-associated processes cause DNA double-strand breaks and translocations in neural stem/progenitor cells. Proc Natl Acad Sci USA. 113:pp. 2258–2263. 2016; View Article : Google Scholar : PubMed/NCBI
15	Ceccaldi R, Rondinelli B and D'Andrea AD: Repair pathway choices and consequences at the double-strand break. Trends Cell Biol. 26:52–64. 2016. View Article : Google Scholar : PubMed/NCBI
16	Li JB and Church GM: Deciphering the functions and regulation of brain-enriched A-to-I RNA editing. Nat Neurosci. 16:1518–1522. 2013. View Article : Google Scholar : PubMed/NCBI
17	Witzany G: The agents of natural genome editing. J Mol Cell Biol. 3:181–189. 2011. View Article : Google Scholar : PubMed/NCBI
18	Grewe F, Viehoever P, Weisshaar B and Knoop V: A trans-splicing group I intron and tRNA-hyperediting in the mitochondrial genome of the lycophyte Isoetes engelmannii. Nucleic Acids Res. 37:5093–5104. 2009. View Article : Google Scholar : PubMed/NCBI
19	Castandet B, Choury D, Bégu D, Jordana X and Araya A: Intron RNA editing is essential for splicing in plant mitochondria. Nucleic Acids Res. 38:7112–7121. 2010. View Article : Google Scholar : PubMed/NCBI
20	Zhang X, Maity T, Kashyap MK, Bansal M, Venugopalan A, Singh S, Awasthi S, Marimuthu A, Jacob HK Charles, Belkina N, et al: Quantitative tyrosine phosphoproteomics of Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor-treated lung adenocarcinoma cells reveals potential novel biomarkers of therapeutic response. Mol Cell Proteomics. 16:891–910. 2017. View Article : Google Scholar : PubMed/NCBI
21	McGranahan N and Swanton C: Clonal heterogeneity and tumor evolution: Past, present, and the future. Cell. 168:613–628. 2017. View Article : Google Scholar : PubMed/NCBI
22	Gao D, Herman JG and Guo M: The clinical value of aberrant epigenetic changes of DNA damage repair genes in human cancer. Oncotarget. 7:37331–37346. 2016. View Article : Google Scholar : PubMed/NCBI
23	King MC, Marks JH and Mandell JB; New York Breast Cancer Study Group, : Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science. 302:643–646. 2003. View Article : Google Scholar : PubMed/NCBI
24	Yu H, Li H, Cui Y, Xiao W, Dai G, Huang J and Wang C: The mRNA level of MLH1 in peripheral blood is a biomarker for the diagnosis of hereditary nonpolyposis colorectal cancer. Am J Cancer Res. 6:1135–1140. 2016.PubMed/NCBI