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胞质NPM1突变蛋白与AKT的相互作用及其对急性髓系白血病细胞增殖的调控

, PP. 2267-2271

Keywords: 白血病,核仁磷酸蛋白,AKT,增殖

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Abstract:

目的探讨细胞质中核仁磷酸蛋白A型突变体(NPM1mutantA,NPM1mA)与AKT的相互作用,观察NPM1mA联合AKT对白血病细胞增殖的影响。方法免疫共沉淀实验观察胞质蛋白NPM1mA与AKT的相互作用。通过RNA干扰技术抑制NPM1突变阳性的OCI/AML3白血病细胞株中NPM1突变蛋白的表达。不同浓度AKT抑制剂(AKTINHIBITORⅣ,AKTⅣ)处理白血病细胞抑制磷酸化AKT蛋白表达。CCK-8法检测细胞体外增殖能力。结果胞质NPM1mA能够与内源性的AKT蛋白相互结合。干扰NPM1后,OCI/AML3细胞中NPM1mA和野生NPM1蛋白表达明显下降(P<0.05),白血病细胞的体外增殖能力亦明显降低(P<0.05)。AKTⅣ处理后,白血病细胞体外增殖较未处理细胞显著下降(P<0.05)。若NPM1沉默合并AKTⅣ处理,则OCI/AML3细胞干扰组体外增殖明显降低(P<0.05)。结论在NPM1突变的白血病细胞中,胞质NPM1mA能够与AKT相互结合,并参与调控白血病细胞的增殖。

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