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慢性粒细胞性白血病中Bim蛋白表达及调控研究

Expression and regulation of Bim protein in chronic myelogenous leukemia

  • 摘要: 目的 : 研究慢性粒细胞性白血病(CML)中Bim蛋白表达及调控。 方法 : 应用患者外周血或骨髓分离培养原代白血病细胞,设立对照组,通过Western blotting、免疫化学、实时定量PCR,检测两组对照细胞中Bim蛋白表达水平及mRNA水平,并加入BCR/ABL抑制剂伊马替尼后对Bim蛋白表达的影响。 结果 : Bim在正常骨髓细胞中持续表达,在CML患者骨髓细胞中表达下降,两者有显著性差异(P<0.05),而相应的Bim-mRNA水平也有显著差异(P<0.05);伊马替尼能增加Bim蛋白表达及mRNA转录的能力,且呈剂量与时间依赖性;同时发现Bim蛋白表达水平与CML患者白血病细胞与正常骨髓细胞的百分比呈负相关(r=0.8491,P<0.05)。 结论 : Bim是Bc1-2家族的促凋亡因子,它的表达下降在CML发生中具重要作用,BCR/ABL被抑制后Bim蛋白表达上调可能具特别意义,研究Bim诱导的凋亡可为今后的临床应用奠定理论基础。

     

    Abstract: Aim :To investigate the expression and the regulation of Bim protein in leukemic cell of patient with chronic myelognous leukemia(CML). Methods :The primary leukemic cells from the peripheral blood or bone marrow of patients with CML were isolated and cultured.The expression of Bim in the present or absence of imatinib(BCR/ABL inhibitor) was detected by the Western blotting,immunohistochemical analysis and real-time quantitative PCR. Results :Bim was consecutively expressed in normal bone marrow,but significantly decreased in the bone marrow of patients with CML(P<0.05).Imatinib significantly enhanced Bim mRNA transcription and expression in the manner of time- and dose-dependence.Moreover,there was reverse correlation between Bim protein level and the percent of leukemic cell in bone marrow(r=0.849 1,P<0.05). Conclusion :Bim is the Bcl-2 family pro-apoptitic factor.The decreased expression of Bim could be vital in the CML,Bim protein up-expression following the suppression of BCR/ABL might be of importance in investigation of the Bim-induced apoptosis for potential clinical therapy.

     

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