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SHIP (SH2domaincontaininginositol5′ phosphatase)基因主要在造血细胞表达 ,并在造血细胞的发生发育中发挥关键的负调节作用。本研究旨在评价SHIP基因突变在白血病发病中的作用。利用RT PCR、SSCP及DNA序列分析技术检测了 32例急性髓细胞白血病、9例急性淋巴细胞白血病及正常对照骨髓或外周血标本中SHIP基因表达及突变情况。RT PCR显示所有标本中都有SHIP基因表达 ,2 2 % (7/32 )AML和 12 % (1/9)ALL标本中存在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 (CR)后消失 ,而且其发病时的白血病细胞在体外随着IL 3的刺激其Akt的磷酸化明显增加。结论 :本研究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 ,它很可能做为一个抑癌基因通过负性调节PI3K/Akt信号通路发挥作用。
SHIP (SH2) is mainly expressed in hematopoietic cells and plays a key negative regulatory role in the development of hematopoietic cells. This study was designed to evaluate the role of SHIP mutations in the pathogenesis of leukemia. The expression and mutation of SHIP gene in 32 cases of acute myeloid leukemia, 9 cases of acute lymphoblastic leukemia and normal control bone marrow or peripheral blood samples were detected by RT PCR, SSCP and DNA sequence analysis. RT-PCR showed SHIP gene expression in all samples, SHIP gene mutation was present in 2% (7/32) AML and 12% (1/9) ALL samples, of which 1 Missense mutation, and complete remission (CR) disappeared, and its onset of leukemia cells in vitro with IL 3 stimulation Akt phosphorylation increased significantly. CONCLUSIONS: This study, for the first time, found that the SHIP gene mutation in acute leukemia cells suggests that the SHIP gene mutation may be related to the pathogenesis of leukemia. In hematopoietic cells, it may play a role as a tumor suppressor gene through negative regulation of PI3K / Akt signaling pathway .