动态观察慢性髓性白血病患者β-catenin变化与细胞遗传学疗效的关系

Dynamic observations of beta-catenin in chronic myeloid leukemia and its relationship with cytogenetic response

目的检测β-catenin在慢性髓性白血病(CML)各期中的表达情况,并动态观察CML患者β-catenin变化与细胞遗传学疗效的关系,为临床更合理制定个体化治疗方案提供依据。方法采用RT-PCR和Westernblotting,检测β-catenin在99例CML患者骨髓单个核细胞中mRNA和蛋白质水平的表达;94例CML患者服用伊马替尼前及后一年内每3月FISH检测bcr/abl融合基因及蛋白质水平的表达,分析β-catenin变化与细胞遗传学疗效的关系。结果 CML急变期、加速期患者β-catenin的表达明显增高(P<0.001),而慢性期与正常人无明显差别(P>0.05);β-catenin持续阴性患者主要细胞遗传学缓解率明显高于β-catenin持续阳性或转为阳性的患者(P<0.001)。结论 CML疾病进展阶段β-catenin的表达明显升高,β-catenin表达持续增高或转为阳性提示伊马替尼疗效可能不佳,应尽早采取其他治疗措施以提高缓解率。

Objective To investigate the changes in the expression ofbeta-catenin in patients with chronic mycloid leukemia （CML） in different phases, and explore the relationship between beta-catenin and the cytogenetic response to ima＇tmib mesylate. Methods Beta-catenin mRNA and protein expressions were detected by RT-PCR and Western blotting in the bone marrow mononuclear cells （BMMNCs） from 99 CML patients. The expressions of BCR-ABL fusion gene at both the mRNA and protein levels were detected by fluorescence in situ hybridization （FISH） in 94 patients before and during the one-year treatment with imatinib mesylate at the interval of 3 months, and the relationship between beta-catenin and cytogenetic response to imatinib mesylate was analyzed. Results The expression of beta-catenin increased significantly in patients with blast crisis and accelerated phase （P〈0.001）, but showed no significant difference between normal subjects and CML patients in the chronic phase （P〉0.05）. The main cytogenetic remission rate was significantly higher in patients who were consistently negative for beta-catenin than in those consistently posiyive for beta-catenin or those with a positive transformation （P〈0.001）. Conclusion Beta-catenin overexpression in the progression of CML, consistent high level of beta-catenin or a positive transformation may, indicate a poor resnonse to imatinib, and early measures should be taken to increase the remission rate.