凋亡调控基因Mcl-1在T细胞性淋巴瘤中的表达及临床意义

背景与目的:T细胞性非霍奇金淋巴瘤(T-cell non-Hodgkin's lymphoma,T-NHL)预后不良,有体外研究表明淋巴瘤细胞株的髓细胞白血病1(myeloid cellleukemia-1,Mcl-1)基因过表达能够拮抗放射和药物诱导的细胞凋亡.本研究探讨Mcl-1在各类型T-NHL中的表达及其与治疗反应和预后的关系.方法:收集临床资料完整的各类型T-NHL病例72例,回顾性分析其临床特点、治疗经过和随访结果,免疫组化染色方法检测Mcl-1表达,并进行相关性分析.结果:Mcl-1在T淋巴母细胞性NHL(precursor T lymphoblastic lymphoma,T-LBL)、间变T细胞性NHL(anaplastic large T-cell lymphoma,ALCL)和其他外周T细胞性NHL(peripheral T-cell lymphoma,PTL)中的弱阳性率分别为44.4%、0%和18.9%,阳性率分别为0%、100%和49.1%(P=0.000).Mcl-1在T-LBL中呈胞浆均匀一致的浅染色,在ALCL中呈核周块状棕黄色强染色.Mcl-1阳性与弱阳性/阴性PTL患者的中位总生存期(overall survival,OS)分别＞32个月和15个月(P=0.007),对化疗有效率分别为75%和53%(P=0.18),多因素分析结果显示国际预后指数(international prognostic index,IPI)和Mcl-1阳性为PTL的独立预后因素;Mcl-1阴性与弱阳性T-LBL患者的中位OS分别为21个月和7个月(P=0.58).结论:不同病理亚型的T-NHL的Mcl-1表达差异具有显著性.Mcl-1在ALCL呈特征性高表达.PTL中Mcl-1阳性患者预后优于阴性/弱阳性患者.

Expression and clinical significance of Mcl-1 in T-cell non-Hodgkin's lymphoma

BACKGROUND & OBJECTIVE: The prognosis of T-cell non-Hodgkin's lymphoma (T-NHL) is poor. Overexpression of myeloid cell leukemia-1 (Mcl-1) gene could inhibit irradiation- and drug-induced apoptosis in several lymphoma cell lines. This study was to detect the expression of Mcl-1 in T-NHL of various subtypes, and explore its correlation to clinicopathologic features and prognosis of T-NHL. METHODS: The expression of Mcl-1 protein in 72 specimens of T-NHL was detected by immunohistochemistry. The clinical features, treatments, and outcomes of the T-NHL patients were analyzed retrospectively. RESULTS: The weak positive rates of Mcl-1 were 44.4% in precursor T lymphoblastic lymphoma (T-LBL), 0% in anaplastic large T-cell lymphoma (ALCL), and 18.9% in other peripheral T-cell lymphoma (PTL); the positive rates were 0%, 100%, and 49.1%, respectively (P<0.001). Weak diffuse cytoplasmic staining of Mcl-1 was detected in T-LBL, and strong cytoplasmic staining with perinuclear accentuation was detected in ALCL. The overall survival time was significantly longer in the PTL patients with high Mcl-1 expression than in the PTL patients with weak/negative Mcl-1 expression (>32 months vs. 15 months, P=0.007), and longer in the T-LBL patients without Mcl-1 expression than in the T-LBL patients with weak Mcl-1 expression (21 months vs. 7 months, P=0.58). CONCLUSIONS: The intensities of Mcl-1 expression in T-NHL of various histological subtypes are different. It is specifically highly expressed in ALCL. High expression of Mcl-1 is correlated to better prognosis of PTL.