Smad4在白血病细胞中表达的初步研究

Expression of Smad4 in Leukemia Cells

TGF-β信号的缺失与许多组织的恶性增生有关,Smad4是该通路的重要蛋白,其缺失或突变与多种癌症相关。本研究目的主要是探讨细胞浆信息传递介质Smad4在白血病细胞中的定位及表达。分离白血病病人骨髓单个核细胞,镜下鉴定白血病细胞数量达90%以上,应用免疫组织化学技术检测白血病细胞中Smad4蛋白的表达。结果表明Smad4蛋白主要表达于细胞核中,部分表达于胞浆中,35例白血病病人中6例急性淋巴细胞性白血病患者Smad4无表达,包括L11例,L31例,L24例;7例急性非淋巴细胞性白血病(1例M0,1例M1,2例M2a,1例M3a,1例M4b,1例M6)和1例慢性粒细胞性白血病患者白血病细胞中也无Smad4表达,其余病人白血病细胞中均表达Smad4。结论Smad4主要定位于细胞核中,在部分白血病细胞中无表达,Smad4基因或功能的改变可能与人类AML的发生有关。

Loss of transforming growth factor （TGF） -β signaling has been implicated in malignant transformation of various tissues. Smad4 plays a central role in the signal transduction of TGF-β. Deletion or mutation of Smad4 has been described in a number of cancers. This study was aimed to investigate a potential role of Smad4 in leukemia including its expression and location in blast cells. The mononuclear cells were separated from bone marrow of leukemia patients. The samples, blast cells of which were more than 90% in mononuclear cells, were selected. The expression and location of Smad4 protein were analyzed by immunohistochemistry methods. The results showed that the Smad4 protein located mainly in nucleus, part of this protein located in cytoplasma, the expressions of Smad4 were not detected in 6 out of 9 ALL patients, in 7 out of 24 AML patients and in 1 out of 2 CML patients; these leukemia patients, in whose cells the expression of Smad4 was not detected, included one L1 and one L3 , four L2, one M0, one M1, two M2a, one M3a, one M4b, one M6 and one CML. In conclusion, the Smad4 protein was mainly in nucleus, the deletion or functional change of Smad4 may related with the pathogenesis of human AML.