bcl-2基因表达在慢性粒细胞白血病急变中的意义

Expression of bcl 2 gene in the evolution of chronic myelogenous leukemia to blast crisis and its implication

目的探讨ｂｃｌ２基因表达在慢性粒细胞白血病（ＣＭＬ）急变中的生物学意义。方法采用碱性磷酸酶抗碱性磷酸酶免疫复合物方法和地高辛标记探针原位杂交技术检测各期ＣＭＬ患者６０例新鲜骨髓标本中ＢＣＬ２蛋白和ｂｃｌ２ｍＲＮＡ的表达，并对其中１９例标本进行流式细胞术分析骨髓细胞凋亡率及细胞周期。结果初诊和治疗后ＣＭＬ中ｂｃｌ２基因表达相近，但明显低于急变时。ｂｃｌ２ｍＲＮＡ表达与蛋白表达基本一致。ｂｃｌ２基因高表达与ＣＭＬ患者外周血血红蛋白、血小板、幼稚细胞及骨髓不成熟细胞比例相关。加速／急变期ＣＭＬ细胞凋亡率明显低于慢性期，但细胞周期无明显变化。结论ＣＭＬ急变时ｂｃｌ２基因表达增高，骨髓细胞凋亡率降低，这些现象部分地阐明了ＣＭＬ急变预后不良的机制，也为ＣＭＬ急变的早期诊断和治疗提供了实验依据。

Objective To investigate the expression of bcl 2 gene and cell apoptosis and cell cycle in bone marrow of chronic myelogenous leukemia (CML). Methods APAAP assay and in situ hybridization were used for the expression of BCL 2 protein and bcl 2 mRNA in fresh bone marrow samples from 60 cases of CML. Flow cytometry was used to assess the extent of apoptosis and cell cycle percentage. Results The expression of bcl 2 gene had no statistical difference between CMLs at presentation and in chronic phase, but was much lower in blast crisis (P<0.05). The percentage of bcl 2 mRNA positive cells was consistent with BCL 2 protein expression. In addition, BCL 2 protein was related to the Hb levels, BPC,and immature cells in the peripheral blood and bone marrow.Notably, the extent of apoptosis in accelerated phase/blast crisis was much lower than that in chronic phase(P=0.028), while the cell cycle had no difference. Conclusion High level of bcl 2 gene expression and low extent of apoptosis in bone marrow cells of CML might partially be the mechanism of poor prognosis of blast crisis, and this provides a new experimental basis for early diagnosis and treatment of CML blast crisis.