依托泊苷对伊马替尼体内清除慢性髓性白血病干细胞的作用研究

Effect of Etoposide on Elimination of Chronic Myeloid Leukemia Stem Cells by Imatinib in Vivo

目的:探讨依托泊苷(ETO)对伊马替尼体内清除慢性髓性白血病干细胞的作用。方法:以SCL-t TA/BCRABL小鼠为慢性髓性白血病动物模型,采用流式细胞术检测ETO单独或联合伊马替尼治疗慢性髓性白血病小鼠和正常FVB小鼠后,对小鼠骨髓和脾脏中白血病干细胞和外周血中性粒细胞数目的影响。结果:ETO和伊马替尼联合治疗后,SCL-t TA/BCR-ABL小鼠骨髓白血病干细胞数及比例、外周血中性粒细胞比例均明显下降,且下降的程度比两者单用更显著。在野生型FVB小鼠中,ETO和伊马替尼联合治疗对骨髓Lin-Sca1^(+)c-kit^(+)细胞数和比例、脾脏中性粒细胞比例无明显影响。结论:ETO在体内具有选择性增强伊马替尼靶向清除慢性髓性白血病干细胞的作用。

Objective:To investigate the effect of etoposide(ETO)on elimination of chronic myeloid leukemia(CML)stem cells by imatinib mesylate(IM)in vivo.Methods:SCL-tTA/BCR-ABL mice were used as CML animal model.Flow cytometry was used to assess the effect of ETO alone or in combination with IM on the number of leukemia stem cell(LSC)in bone marrow and spleen,and peripheral blood neutrophils in CML mice and normal control FVB mice.Results:The results showed that in CML mice,the number and proportion of LSC in bone marrow and the proportion of neutrophils in peripheral blood decreased significantly after ETO and IM combined treatment,and the degree of decrease was more significant than that of both alone.While in wild type FVB mice,the combination of ETO and IM showed no significant effect on the number and proportion of LSK cells in bone marrow and the proportion of neutrophils in spleen.Conclusion:ETO can selectively enhance elimination of CML LSC by IM in vivo.