FLT3-的AML细胞对PKC412体外敏感性的初步研究

摘要

Objective:To explore the clinical value of PKC412 (midostaurin) in treatment of AML patients with FLT3-.Methods:The bone marrow or peripheral blood were collected and heparinized from 21 newly diagnosed FLT3-AML patients,then the mononuclear cells from bone marrow or peripheral blood were isolated by densitygradient method.The sensitivity of leukemia cells to PKC412 of 8 concentration in vitro was detected by ATP-bioluminescence-tumor chemosensitivity assay (ATP-TCA),and the relationship among sensitivity results in vitro,risk stratification and therapeutic efficacy was analyzed.Results:The leukemia cells of 21 patients with AML displayed different sensitivities to PKC412 in vitro.The rate of sensitivity in vitro was 42.9％,and sensitive concentration in vitro were between 1 μmol/L and 5 μmol/L.There was no significant relationship between risk stratification and sensitivity results of PKC412 in vitro.There was also no significant relationship between clinical efficacy and sensitivity results of PKC412 in vitro.The survival of patients in low-risk and intermediate-risk groups was better than that of patients in high-risk groups (P =0.015).Conclusion:PKC412 can be one of the effective therapeutic method for AML patients without FLT3 mutation.The sensitivity of leukemia cells to PKC412 may become a prognostic marker for evaluating clinical efficacy of PKC412,which is independent of other factors.%目的:探索PKC412(midostaurin,米哚妥林)在FLT3-AML患者治疗中的价值.方法:无菌采集21例FLT3-的初治AML患者骨髓血或外周血肝素抗凝,应用密度梯度离心法分离单个核细胞,采用三磷酸腺苷生物荧光肿瘤体外药敏检测技术(ATP bioluminescence-tumor chemosensitivity assay,ATP-TCA)测定白血病细胞体外对8种浓度PKC412的敏感性,并分析其体外药敏结果、危险度分层及临床疗效三者之间的关系.结果:21例AML患者的白血病细胞在体外对PKC412的反应不相同,体外敏感率为42.9％,体外敏感浓度为1-5 μmol/L.PKC412体外药敏结果与患者危险度分层之间无相关性,与临床疗效之间也无相关性.低、中危组患者的存活率著优于高危组患者(P=0.015).结论:PKC412可能是FLT3-初治AML的有效治疗手段之一;白血病细胞对PKC412的敏感性有可能成为判断PKC421疗效的独立预测指标.