Nilotinib rapidly reverses breakpoint cluster region-Abelson oncogene fusion gene and M244V mutations in a patient with chronic myelogenous leukemia: A case report

Shen,Xuliang; Zhang,Meixiang; Shen,Yifan; Shi,Wenzhi; Liu,Wei; Wei,Wu

doi:10.3892/etm.2015.2707

Nilotinib rapidly reverses breakpoint cluster region-Abelson oncogene fusion gene and M244V mutations in a patient with chronic myelogenous leukemia: A case report

Authors:
- Xuliang Shen
- Meixiang Zhang
- Yifan Shen
- Wenzhi Shi
- Wei Liu
- Wu Wei
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Affiliations: Department of Hematology, Heping Hospital of Changzhi Medical College, Changzhi, Shanxi 046000, P.R. China, Department of Hematology, Beijing Rehabilitation Hospital of Capital Medical University, Beijing 100144, P.R. China, Department of Hematology, Heji Hospital of Changzhi Medical College, Changzhi, Shanxi 046000, P.R. China
Published online on: August 24, 2015 https://doi.org/10.3892/etm.2015.2707
Pages: 1479-1482

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Abstract

Chronic myelogenous leukemia (CML) is a condition characterized by a balanced genetic translocation, t (9;22) (q34;q11.2), which leads to a fusion of the Abelson oncogene (ABL) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is referred to as the Philadelphia chromosome. At a molecular level, this translocation results in the formation of the BCR‑ABL fusion oncogene, which translates into a BCR‑ABL oncoprotein. Imatinib, nilotinib and dasatinib are three tyrosine kinase inhibitors that have been approved by the US Food and Drug Administration for the treatment of patients diagnosed with CML in the chronic phase (CML‑CP). The present study describes the case of a patient with imatinib‑resistant CML who, following two months of treatment with nilotinib, no longer exhibited detectable BCR‑ABL fusion genes or M244V mutations. This suggests that nilotinib may be effective for treating CML cases in which the BCR‑ABL fusion protein has an M244V mutation.

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1	Rowley JD: Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature. 243:290–293. 1973. View Article : Google Scholar : PubMed/NCBI
2	Jabbour E and Kantarjian H: Chronic myeloid leukemia: 2014 update on diagnosis, monitoring and management. Am J Hematol. 89:547–556. 2014. View Article : Google Scholar : PubMed/NCBI
3	Kantarjian H, Shah NP, Hochhaus A, et al: Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 362:2260–2270. 2010. View Article : Google Scholar : PubMed/NCBI
4	Saglio G, Kim DW, Issaragrisil S, et al: ENESTnd Investigators: Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 362:2251–2259. 2010. View Article : Google Scholar : PubMed/NCBI
5	Druker BJ, Guilhot F, O'Brien SG, et al: IRIS Investigators: Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 355:2408–2417. 2006. View Article : Google Scholar : PubMed/NCBI
6	Osborn M and Hughes T: Managing imatinib resistance in chronic myeloid leukaemia. Curr Opin Hematol. 17:97–103. 2010. View Article : Google Scholar : PubMed/NCBI
7	Jabbour E, Branford S, Saglio G, et al: Practical advice for determining the role of BCR-ABL mutations in guiding tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia. Cancer. 117:1800–1811. 2011. View Article : Google Scholar : PubMed/NCBI
8	Hochhaus A, La Rosée P, Müller MC, et al: Impact of BCR-ABL mutations on patients with chronic myeloid leukemia. Cell Cycle. 10:250–260. 2011. View Article : Google Scholar : PubMed/NCBI
9	Kim WS, Kim D, Kim DW, et al: Dynamic change of T315I BCR-ABL kinase domain mutation in Korean chronic myeloid leukaemia patients during treatment with Abl tyrosine kinase inhibitors. Hematol Oncol. 28:82–88. 2010.PubMed/NCBI
10	Qin Y, Chen S, Jiang B, et al: Characteristics of BCR-ABL kinase domain point mutations in Chinese imatinib-resistant chronic myeloid leukemia patients. Ann Hematol. 90:47–52. 2011. View Article : Google Scholar : PubMed/NCBI
11	Ernst T, Erben P, Müller MC, et al: Dynamics of BCR-ABL mutated clones prior to hematologic or cytogenetic resistance to imatinib. Haematologica. 93:186–192. 2008. View Article : Google Scholar : PubMed/NCBI
12	Strhakova L, Bujalkova MG, Hojsikova I, et al: Use of direct sequencing for detection of mutations in the BCR-ABL kinase domain in Slovak patients with chronic myeloid leukemia. Neoplasma. 58:548–553. 2011. View Article : Google Scholar : PubMed/NCBI
13	Bagadi S, Saikia T, Pany A and Das B: Analysis of ABL kinase domain mutations conferring resistance to tyrosine kinase inhibitors in chronic myeloid leukemia cases from India. Clin Lab. 57:619–623. 2011.PubMed/NCBI
14	Awidi A, Ababneh N, Magablah A, et al: ABL kinase domain mutations in patients with chronic myeloid leukemia in Jordan. Genet Test Mol Biomarkers. 16:1317–1321. 2012. View Article : Google Scholar : PubMed/NCBI
15	Huang Q, Du X, Zhang QX and Zhuo JC: Establishment of real-time fluorescent quantitative polymerase chain reaction for rapid detection of M244V mutation in kinase domain of BCR-ABL fusion gene. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 22:1728–1734. 2014.(In Chinese). PubMed/NCBI
16	Tanneeru K and Guruprasad L: Ponatinib is a pan-BCR-ABL kinase inhibitor: MD simulations and SIE study. PLoS One. 8:e785562013. View Article : Google Scholar : PubMed/NCBI
17	Preuner S, Mitterbauer G, Mannhalter C, et al: Quantitative monitoring of BCR/ABL1 mutants for surveillance of subclone-evolution, -expansion and -depletion in chronic myeloid leukaemia. Eur J Cancer. 48:233–236. 2012. View Article : Google Scholar : PubMed/NCBI
18	Florek I, Sacha T, Zawada M, et al: Implementation of direct sequencing as a method of ABL gene mutations analysis in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitor. Przegl Lek. 67:1292–1297. 2010.(In Polish). PubMed/NCBI
19	Soverini S, Colarossi S, Gnani A, et al: GIMEMA Working Party on Chronic Myeloid Leukemia: Contribution of ABL kinase domain mutations to imatinib resistance in different subsets of Philadelphia-positive patients: by the GIMEMA Working Party on Chronic Myeloid Leukemia. Clin Cancer Res. 15:7374–7379. 2006. View Article : Google Scholar
20	Anand M, Khorashad J, Marin D, Apperley JF, Goldman JM and Kaeda JS: Varying response to escalating the dose of imatinib in patients with CML who ‘acquire’ a BCR-ABL M244V mutant allele. Blood. 108:2881–2882. 2006. View Article : Google Scholar : PubMed/NCBI