服用伊马替尼慢性粒细胞白血病患者hOCT1表达的变化

Expression of hOCT1 in Patients with Chronic Myelogeneous Leukemia Treated by Imatinib Mesylate

目的动态检测慢性粒细胞白血病(CML)患者服用伊马替尼(IM)前后的hOCT1基因表达及其变化,探讨hOCT1基因表达与疾病的阶段、病程及伊马替尼疗效的关系。方法收集四川大学华西医院血液科CML30例(20例慢性期、10例进展期)患者的骨髓或外周血标本共63份,按伊马替尼疗效分为有反应(佳+次佳)及失败两组。采用半定量RT-PCR方法进行hOCT1基因mRNA水平检测,并结合临床表现、实验室检查和细胞遗传学结果,分析hOCT1水平变化与疾病阶段及伊马替尼疗效相关性。结果①30例CML患者,基线和治疗后hOCT1相对表达量分别为0.5110±0.1629,0.5207±0.1909,差异无统计学意义(P=0.5840)。②20例慢性期及10例进展期CML患者的基线hOCT1水平分别为0.5525±0.1985,0.4490±0.1717,差异无统计学意义(P=0.1090)。提示CML疾病分期可能对hOCT1水平没有影响。③服用伊马替尼3、6、9、12及15个月患者的hOCT1水平,差异无统计学意义(P=0.3412),提示服用伊马替尼疗程长短与hOCT1的表达没有关系。④伊马替尼疗效有反应组(佳+次佳)15例患者与失败组5例患者hOCT1基线水平分别为0.5820±0.1460,0.4640±0.1781,P=0.127。提示伊马替尼疗效与基线hOCT1水平无明显相关性。⑤16例慢性期CML患者伊马替尼治疗后hOCT1较基线hOCT1升高,分别为0.5207±0.1909,0.5110±0.1629,P=0.001。但hOCT1增加与BCR-ABL降低值无相关性。结论CML疾病的不同分期、不同病程、不同伊马替尼疗效患者的基线hOCT1 mRNA水平差异均无统计学意义,说明hOCT1 mRNA基线水平与伊马替疗效无关。

Objective To measure the expression of hOCT1 gene in patients with Chronic Myelogeneous Leukemia （CML） and to explore its role in the progress of the disease and responding to Imatinib Mesylate （IM） treatment. Methods Sixty three peripheral blood or bone marrow samples were taken from 30 patients with CML （20 in chronic phase,10 in advanced phase）. The samples were divided into two groups： responding （optimal and suboptimal） and non-responding according to effectiveness of the IM treatment. The mRNA levels of hOCT1 gene were detected with RT-PCR （SQ-PCR）, 3, 6, 9, 12 and 15 months after the IM therapy. The associations between hOCT1 gene levels and clinical presentations, laboratory indicators and cytogenetic findings were analysed. Results No significant difference in the expression levels of hOCT1 gene was found before and after the IM treatment （0. 5110±0. 1629 vs 0. 5207±0. 1909, P=0. 5840）. No significant difference in the expression levels of hOCT1 genes was found between the patients in chronic phase and the patients in advanced phase before the IM treatment （0. 5525±0. 1985 vs 0. 4490±0. 1717, P=0. 1090）. The levels of hOCT1 did not have significant changes 3, 6, 9, 12 and 15 months after the IM treatment （P=0. 3412）. No significant difference in the expression levels of hOCT1 genes was found between the 15 patients with optimal and suboptimal responding to IM and the 5 patients with no responding to IM （0. 5820±0. 1460 vs 0. 4640±0. 1781, P=0. 127）. Although the hOCT1 levels of the 16 chronic patients increased after IM treatment compared to the baseline （0. 5207±0. 1909 vs 0. 5110±0. 1629, P=0. 001）, there was no significant correlation between the increase of hOCT1 and the decrease of BCR-ABL （P= 0. 821）. Conclusion hOCT1 has no association with the stage and course of CML, nor with the effectiveness of IM therapy.