伊马替尼对BCR/ABL融合基因阳性的急性巨核细胞白血病原代细胞凋亡作用的研究

Apoptosis Effect of Imatinib on Primary Acute Megakaryocytic Leukemia Cells Expressing BCR/ABL

目的:研究酪氨酸激酶抑制剂伊马替尼(imatinib)对BCR/ABL融合基因阳性的急性巨核细胞白血病原代细胞凋亡的作用,探讨急性巨核细胞白血病的治疗。方法:报告1例急性巨核细胞白血病的临床及实验室特征;应用骨髓细胞直接法和24h短期培养法制备染色体和R显带技术进行细胞遗传学分析;多重RTPCR方法同时检测29种白血病融合基因。取患者骨髓白血病细胞,台盼蓝拒染实验观察伊马替尼对细胞生长曲线的影响;流式细胞仪分析细胞周期。结果:①该例患者的染色体核型为46,XX,t(1;16)(q22;q22),未见Ph染色体;表达BCR/ABLb2a2mRNA,临床治疗效果差,生存期短。②伊马替尼可以抑制该原代白血病细胞的生长,促其凋亡,使大部分细胞受阻于G0/G1期。结论:伊马替尼可以诱导BCR/ABL阳性急性巨核细胞白血病原代细胞的凋亡。

Objective：To study the apoptosis effect of imatinib, an inhibitor of tyrosine kinase on primary acute Megakaryocytic Leukemia （AMKL）cells expressing BCR/ABL. Methods： Detailed clinical manifestations and laboratory features of a patient with acute megakaryocytic leukemia were presented. Bone marrow cell chromosome karyotypic analysis was carried out with direct method, short-term culture and R-banding technique. Peripheral blood samples from the patient were analyzed with a novel multiplex nested RT-PCR. Primary cells were grown in the absence or presence of imatinib. The percentage of viable cells was determined by trypan blue exclusion. Cell cycle distribution was studied after DNA staining by propidium iodide. Results： ①The patients karyotype was 46, XX, t （1 ; 16）（q22 ; q22）, but Ph chromosome was negative. The primary cells expressed BCR/ABLb2a2 mRNA. Outcome was poor for this patient and survival was short. ② Imatinib could inhibit the primary cells growth and induce primary cells apoptosis. Imatinib blocked cells mainly in the G0/G1 phase of the cell cycle. Conclusion： Imatinib can induce apoptosis of the primary AMKL cells expressing BCR/ABL.