急性白血病细胞SHIP基因的突变分析  

Mutation analysis of SHIP gene in acute leukemia

作　　者：罗建民[1] 刘泽林[1] 郝洪岭[1] 王福旭[1] 董作仁[1] 大野竜三 

机构地区：[1]河北医科大学第二医院血液科,石家庄050000 [2]日本国爱知县癌中心

出　　处：《中华血液学杂志》2004年第7期385-388,共4页Chinese Journal of Hematology

基　　金：国家自然科学基金资助项目 (3 0 2 40 0 11)

摘　　要：目的　评价SHIP基因突变在白血病发病中的作用。方法　利用逆转录 聚合酶链反应(RT PCR)、单链构象多态性 (SSCP)及DNA序列分析技术检测了 4 1例急性白血病患者、5 0名正常人的骨髓或外周血标本、8株白血病细胞系SHIP基因表达及突变情况。结果　RT PCR显示所有标本中都有SHIP基因表达 ,发现 32例急性髓系白血病 (AML)患者中有 7例 (2 2 % )和 9例急性淋巴细胞白血病 (ALL)患者中有 1例 (12 % )存在SHIP基因的突变 ,其中 1例AML患者发病时标本同时存在 2个错义突变 ,而完全缓解后消失。发病时患者的白血病细胞在体外随着IL 3的刺激其Akt磷酸化明显增加。结论　首次发现急性白血病细胞中SHIP基因突变 ,提示SHIP基因的突变可能与白血病发病有关 ,在造血细胞中 。Objective The SH2 domain containing inositol 5 ′ phosphatase (SHIP) is predominately expressed in hematopoietic cells, and is a crucial negative regulator in the development of hematopoietic cells. This paper is to evaluate the role of the SHIP gene in human leukemogenesis. Methods Expression of SHIP gene in bone marrow and /or peripheral blood from 32 patients with acute myeloid leukemia (AML), 9 with acute lymphoblastic leukemia (ALL), as well as human hematopoietic cell lines was analyzed by reverse transcription polymerase chain reaction (RT PCR), single strand conformational polymorphism (SSCP) and DNA sequencing. Results RT PCR showed that all samples expressed SHIP gene. Mutations of SHIP gene were detected in 7 (22%) of 32 AML patients and one (12%) of 9 ALL patients. Interestingly, two missense mutations that had been observed in a AML patient at diagnosis disappeared after complete remission (CR). In addition, in vitro Akt phosphorylation was prolonged and increased following IL 3 stimulation of this patient's cells. Conclusion Our data demonstrate for the first time the mutation of SHIP gene in acute leukemia and suggest a possible role of the mutation of this gene in the development of acute leukemia. SHIP may serve as a tumor suppressor by negatively regulating the PI3K/Akt signaling pathway in hematopoietic cells.

关 键 词：急性白血病 细胞SHIP基因 基因突变 AML 

分 类 号：R733.7[医药卫生—肿瘤] R394[医药卫生—临床医学]