ABL激酶区突变在中国汉族人群伊马替尼耐药Ph＋急性淋巴细胞白血病与慢性髓性白血病患者中的分布及特点比较  

The different characteristics of ABL kinase domain mutation in the Chinese Han nationality imatinib resistant Philadelphia chromosome-positive acute lymphoblastic leukemia and chronic myeloid leuke-mia

作　　者：沈宏杰[1] 何军[1] 邱桥成[1] 岑建农[1] 潘金兰[1] 姚利[1] 丁子轩[1] 陈艳[1] 陈子兴[1] 

机构地区：[1]苏州大学附属第一医院、江苏省血液研究所、卫生部血栓与止血重点实验室,215006

出　　处：《中华血液学杂志》2013年第1期21-25,共5页Chinese Journal of Hematology

基　　金：江苏省医学创新团队及领军人才（LJ201138）;江苏省临床医学中心（ZX201102）;苏州市科技基础设施建设计划（SZS201001）;苏州市科技发展计划（SYSD2011075）

摘　　要：目的分析ABL激酶区突变在中国汉族人群伊马替尼耐药Ph染色体阳性（Ph＋）急性淋巴细胞白血病（ALL）患者中的分布及特点并与慢性髓性白血病（CML）中ABL激酶区突变进行比较。方法研究对象为2010年10月至2012年4月伊马替尼耐药的122例CML患者及21例Ph＋ALL患者。收集CML患者骨髓或外周血单个核细胞及Ph＋ALL患者骨髓白细胞，采用TRIzol法抽提总RNA，检测ABL激酶区突变，并结合骨髓细胞形态学、染色体和融合基因结果分析ABL激酶区突变的分布特点。结果在112例伊马替尼耐药CML患者中检出20个位点23种ABL激酶区突变，突变比例为54．46％（61例），其中P—loop区突变占耐药CML患者的23．21％（26例）。在21例伊马替尼耐药Ph＋ALL患者中检出8个位点10种突变，突变比例为71．43％（15例），其中T315I突变比例最高，占耐药Ph＋ALL患者的28．57％（6例），其次为E255K／V19．05％（4例）和Y253F／H14．29％（3例）。T315I突变在耐药Ph＋ALL患者中的比例显著高于在耐药CML患者中的比例（P：0．001）；Ph＋ALL患者使用伊马替尼后出现ABL激酶区突变时间显著短于CML患者（P〈0．01）；具有额外染色体结构和（或）数目异常的伊马替尼耐药Ph’ALL患者中ABL激酶区突变比例明显高于同组CML患者（P=0．010）。结论ABL激酶区突变在伊马替尼耐药Ph＋ALL与CML患者中的主要类型及分布明显不同。具有额外染色体结构和（或）数目异常的耐药Ph’ALL患者中ABL激酶区突变比例显著高于同组CML患者。Objective To identify the distribution and differentiation of ABL kinase domain mutation in the Chinese Han nationality imatinib resistant chronic myeloid leukemia （CML） and Philadelphia chromo- some-positive acute lymphoblastic leukemia （Ph＋ ALL）. Methods Bone marrow or peripheral blood sam- ples of 112 imatinib resistant CML patients and 21 Ph ＋ ALL patients were obtained from the first affiliated hospital of Soochow university according to local law. Total RNA was extracted from the mononuclear cells using a TRIzol reagent. ABL kinase domain （KD） mutation was detected by direct sequencing. Results Of the 112 imatinib resistant CML patients, 54.46% （61 cases） had ABL KD mutation. Twenty-three mutants were identified in 20 amino acid sites and 23.21% （26 cases） ABL KD mutations were in P-loop region. ABL KD mutations were also detected in 71.43% （15 cases） imatinib resistant Ph＋ ALL patients, with 10 mutations in 8 amino acid sites. The most frequent mutation was T315I （28.57%）, followed by E255K/V （19.05%） and Y253F/H （14.29%）. The frequency of T315I was much higher in imatinib resistant Ph ＋ALL than that in imatinib resistant CML （P = 0. 001 ）. Ph ＋ ALL with additional chromosomal aberrations also had a higher rate of ABL KD mutation than that of CML （P = 0. 010）. Ph ＋ ALL gained ABL KD mutation faster than CML（P 〈 0. 010）. Conclusion Chinese imatinib resistant CML and Ph ＋ ALL patients had differ- ent characteristics in ABL KD mutation. The rate of ABL KD mutation in Ph ＋ ALL with additional chromo- somal aberrations was much higher than that of CML with additional chromosomal aberrations.

关 键 词：白血病 淋巴细胞 急性 白血病 髓样 慢性 费城染色体 ABL激酶区 DNA突变分析 

分 类 号：R733.7[医药卫生—肿瘤]