雷帕霉素治疗酪氨酸激酶抑制剂耐药慢性粒细胞白血病二例并文献复习

Rapamycin for treatment of tyrosine kinase inhibitor-resistant chronic myelogenous leukemia:report of two cases and review of literature

目的探讨使用雷帕霉素治疗无ABL突变的酪氨酸激酶抑制剂(TKI)耐药慢性粒细胞白血病(CML)的效果。方法采用流式细胞术检测江苏省人民医院收治的2例TKI耐药的CML患者CD33阳性细胞中p-mTOR和p-S6的阳性表达情况,并检测体外加用雷帕霉素后对p-mTOR和p-S6阳性表达的影响。结果体外加用雷帕霉素后能够抑制CD33阳性细胞中p-mTOR和p-S6阳性表达;口服雷帕霉素3个月后CD33阳性细胞中p-mTOR和p-S6阳性表达下降,且BCR-ABL融合基因拷贝数也同步降低。结论部分CML患者对TKI耐药可能与mTOR胞内信号途径活化有关。

Objective To investigate the effect of rapamycin in treatment of tyrosine kinase inhibitor(TKI)-resistant chronic myelogenous leukemia(CML)without ABL mutation.Methods Flow cytometry was used to detect the positive expressions of p-mTOR and p-S6 in CD33 positive cells of 2 CML patients with TKI resistance in Jiangsu Province Hospital,and the influence of rapamycin on the positive expressions of p-mTOR and p-S6 in vitro.Results Rapamycin in vitro inhibited the positive expressions of p-mTOR and p-S6 in CD33 positive cells.After 3 months of oral administration of rapamycin,the positive expressions of p-mTOR and p-S6 in CD33 positive cells were decreased,and the copy number of BCR-ABL fusion gene was also decreased simultaneously.Conclusion Part of the resistance of CML patients to TKI may be related to the activation of intracellular signaling pathway of mTOR.