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
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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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Keywords:
- chronic myelogenous leukemia /
- cell apoptosis /
- Bim protein
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