IKZF1突变在慢性粒细胞白血病急变成急性淋巴细胞白血病中的作用

摘要

Objective The new gene mutation as second hit is important for tumor progression,this paper explores the relationship between IKZF1 gene mutation and lymphoblast crisis of chronic myelogenous leukemia.Methods Two hundreds and twelve cases of leukemia patients were selected that treated in Department of Hematology,Peking University First Hospital and Lu Dao Pei Blood and Cancer Center,Hebei Yanda International Hospital from June 2009 to October 2011 as the research object [including 20 acute myelogenous leukemia (AML) cases,156 cases of B-acute lymphocytic leukemia (B-ALL),36 patients with chronic myelogenous leukemia (CML)],and 10 cases of healthy as controls.Firstly,nested PCR was used to amplify cDNA samples of IKZF1 gene from initial treatment patients or blast phase patients.And then the PCR products were detected by agarose gel electrophoresis.Different subtypes of IKZF1 gene could be obtained by sequencing abnormal amplified fragment.Results In 156 cases of B-ALL,43 cases (27.6％) were detected abnormal expression of IKZF1.Twenty cases of AML and 10 healthy control samples were not detected abnormal expression of IKZF1.Thirty cases (79.0％) out of 38 cases of BCR-ABLl-positive B-ALL were detected the IKZF1 abnormal expression and 25 cases were Ik6,2 cases were Ik9,1 cases were Ik7,2 cases were IKZF1 expression missing.In 118 cases of BCR-ABLl-negative B-ALL,13 cases (11.0％) were detected abnormal expression of IKZF1 (all were Ik6).Older patients with acute lymphocytic leukemia had a high rate of IKZF1 gene deletion.In 36 initial treatment and chronic phase CML cases were not detected abnormal expression of IKZF1.Among 12 cases that changed into B-ALL blast crisis from CML,7 cases (58.3％) expressed Ik6.IKZFI abnormal expression was not detected in patients which changed into AML blast crisis from CML.Contusion The IKZF1 geue mutation as second hit is an important factor of CML lymphoblast crisis.%目的 探讨IKZF1基因变异与慢性髓细胞白血病急变的关系.方法 选取北京大学第一医院及陆道培血液肿瘤中心2009年6月至2011年10月就诊的212例白血病[156例急性淋巴细胞白血病(B-ALL)、20例急性髓性白血病(AML)、36例慢性髓细胞白血病(CML)]患者及10名健康对照者为研究对象.采用巢式PCR方法扩增患者初治或急变期标本中IKZF1基因cDNA,PCR后的产物进行电泳检测,对异常扩增片段进行基因测序分析,以确定IKZF1基因的不同亚型.结果 BALL中常有IKZFI异常表达,156例B-ALL中43例(27.6％)出现IKZF1异常表达.20例AML和10名健康对照者标本中均未检测到IKZF1异常表达.BCR-ABL1阳性B-ALL有IKZF1异常表达,38例中有30例(79.0％)增高,其中25例表达Ik6、2例表达Ik9、1例表达Ik7,2例IKZF1表达缺失.BCR-ABL1阴性的118例B-AL中,仅有13例(11.0％) IKZF1异常表达(均为Ik6).CML初治和慢性期标本中均未检测到IKZF1异常表达.CML发生B-ALL急变的12例患者中,7例(58.3％)有Ik6表达；而发生AML急变的CML标本中均无IKZFI异常表达.结论 IKZF1基因变异所致的2次打击是CML急变为B-ALL的一个重要因素.