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学科主题: 临床医学
题名:
Characteristics of BCR-ABL kinase domain point mutations in Chinese imatinib-resistant chronic myeloid leukemia patients
作者: 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
发表日期: 2011
DOI: 10.1007/s00277-010-1039-5
卷: 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
所属项目编号: IRT0702
项目资助者: Ministry of Education of the People&prime ; s Republic of China
WOS记录号: WOS:000285783800008
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57654
Appears in Collections:北京大学第二临床医学院_血液科_期刊论文

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作者单位: Peking Univ, Peoples Hosp, Inst Hematol, Beijing 100044, Peoples R China

Recommended Citation:
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.
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