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学科主题临床医学
Characteristics of BCR-ABL kinase domain point mutations in Chinese imatinib-resistant chronic myeloid leukemia patients
Qin, YaZhen; Chen, ShanShan; Jiang, Bin; Jiang, Qian; Jiang, Hao; Li, JinLan; Li, LingDi; Lai, YueYun; Liu, YanRong; Huang, XiaoJun
关键词Chronic Myeloid Leukemia Imatinib-resistant Bcr-abl Kinase Domain Point Mutations Chinese
刊名ANNALS OF HEMATOLOGY
2011
DOI10.1007/s00277-010-1039-5
90期:1页:47-52
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Hematology
研究领域[WOS]Hematology
关键词[WOS]CHRONIC MYELOGENOUS LEUKEMIA ; CHRONIC-PHASE ; CYTOGENETIC RESPONSES ; MOLECULAR RESPONSES ; BLAST CRISIS ; FOLLOW-UP ; MECHANISMS ; MESYLATE ; CYTARABINE ; INTERFERON
英文摘要

To explore the characteristics of BCR-ABL kinase domain point mutations in Chinese chronic myeloid leukemia (CML) patients, a cohort of 127 patients with hematologic or cytogenetic resistance to imatinib are screened by direct sequencing. Mutations are found in 74 patients (58%). More patients with hematologic resistance show mutations compared to patients with cytogenetic resistance (70% vs 44%, p = 0.002), and more patients with acquired resistance present mutations compared to patients with primary resistance (68% vs 48%, p = 0.031). Frequencies of mutations were similar in early chronic phase (ECP), late chronic phase (LCP), accelerated phase, and blast phase (BP) patients (56%, 58%, 50%, and 69%, respectively; p > 0.05). Overall, 25 mutants are found in 21 amino acid sites, and four of them (I418V, E450A, E453L, and E455K) are first reported here. All patients with these four mutants either progress to or reenter the BP. The most frequent mutant is M244V, followed by Y253H, F359C/V/I, G250E, E255K, and T315I. Only seven patients (9%) have T315I mutants, and all showed hematologic resistance. Three of them were in the ECP and three in the LCP. Look-back studies show that mutants were detected 0-20 (median 7) months ahead of the appearance of clinical resistance in 15 tested patients with acquired resistance. ABL mutations are common in Chinese imatinib-resistant CML patients and are associated with clinical resistance. Chinese patients also seem to have unique profiles in the types and frequencies of some mutants, the disease phases of patients with T315I mutation, and the frequency of mutations in CP patients.

语种英语
WOS记录号WOS:000285783800008
项目编号IRT0702
资助机构Ministry of Education of the People&prime ; s Republic of China
引用统计
被引频次:24[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/57654
专题北京大学第二临床医学院_血液科
北京大学药学院_药事管理与临床药学系
北京大学临床肿瘤学院_移植与免疫治疗病区
作者单位Peking Univ, Peoples Hosp, Inst Hematol, Beijing 100044, Peoples R China
推荐引用方式
GB/T 7714
Qin, YaZhen,Chen, ShanShan,Jiang, Bin,et al. Characteristics of BCR-ABL kinase domain point mutations in Chinese imatinib-resistant chronic myeloid leukemia patients[J]. ANNALS OF HEMATOLOGY,2011,90(1):47-52.
APA Qin, YaZhen.,Chen, ShanShan.,Jiang, Bin.,Jiang, Qian.,Jiang, Hao.,...&Huang, XiaoJun.(2011).Characteristics of BCR-ABL kinase domain point mutations in Chinese imatinib-resistant chronic myeloid leukemia patients.ANNALS OF HEMATOLOGY,90(1),47-52.
MLA Qin, YaZhen,et al."Characteristics of BCR-ABL kinase domain point mutations in Chinese imatinib-resistant chronic myeloid leukemia patients".ANNALS OF HEMATOLOGY 90.1(2011):47-52.
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