伊马替尼对慢性髓性白血病酪氨酸磷酸化的影响

Analysis of the effect of imatinib treatment to tyrosine phosphorylation level of chronic myelocytic leukemia cells

目的研究伊马替尼对慢性髓性白血病(chronic myelogenous leukemia,CML)患者骨髓细胞酪氨酸磷酸化(tyrosine phosphorylation,p-Tyr)水平的影响。方法对2011年1月至2014年12月于本院就诊的47例CML患者(其中24例接受伊马替尼治疗)及6例健康对照者的骨髓细胞进行胞膜CD45和胞质内p-Tyr(PY99)荧光标记,应用流式细胞计量术(flow cytometry,FCM)分析不同病期CML患者的各群细胞p-Tyr水平。结果未经伊马替尼治疗的慢性期(chronic phase,CP)和加速期(accelerated phase,AP)患者的骨髓各群细胞p-Tyr水平均高于对照组,除CP患者的(偏)成熟粒细胞群较对照组的增高差异无显著性(P>0.05)外,其余差异均具有显著性(P<0.05)。应用伊马替尼治疗时间≥12个月的CP患者其骨髓细胞p-Tyr水平低于用药时间<12个月者;用药时间≥12个月的AP患者其幼稚细胞群p-Tyr水平亦低于用药时间<12个月者。结论 CML患者各病期细胞的p-Tyr水平均较高,伊马替尼对CML细胞p-Tyr水平的降低程度随用药时间延长而增强。

Objective To analyze the effect of imatinib treatment to phosphorylation level. Method FCM assay was used to detect tyrosine phosphorylation of different groups of cells from 47 CML samples（24 were treated with imatinib） and 6 normal bone marrow samples. Cells were stained with CD45 and p-Tyr（anti-phosphotyrosine, PY99） monoclonal antibody. Result In patients who had never used imatinib, the tyrosine phosphorylation（p-Tyr） level of different groups of cells from accelerated phase（AP） patients and different groups of cells except for mature neutrophil from chronic phase（CP） was significantly higher than that from normal control. Comparing with samples from CP patients who received imatinib treatment for shorter than 12 months, the p-Tyr level of different groups of cells was lower in samples with imatinib treatment longer than 12 months. In AP patient samples, the p-Tyr level of blasts was lower in long-time imatinib treatment（≥12 months） group than that in short–time treatment group（〈12 months）. Conclusion The p-Tyr level of different groups of cells from different stages patients was higher than that from normal.The downward effect of imatinib to p-Tyr level of leukemia cells from CP samples can be strengthened by prolong drug application time.