大颗粒T淋巴细胞白血病的免疫基因诊断和西罗莫司治疗  

Immunogenetic Diagnosis of Large Granular Lymphocytic Leukemia and Therapy by Sirolimus

作　　者：邢海洲[1] 朱平[1,2] 刘倩[1] 张英[1] 陈艳[1] 胡旸[1] 陈雪[1] 夏君燕[1] 田正芹[1] 龚艺文[2] 

机构地区：[1]北京大学第一医院血液科,北京100034 [2]北京航天总医院血液肿瘤研究所,北京100076

出　　处：《中国实验血液学杂志》2012年第1期26-32,共7页Journal of Experimental Hematology

摘　　要：本研究报告4例大颗粒淋巴细胞白血病(LGLL)的免疫基因诊断及mTOR阻断剂西罗莫司治疗的效果,并结合国内外报道的有较完整资料的256例患者进行分析。LGLL均以外周血淋巴细胞绝对值高、粒细胞减少或(和)贫血为主要表现。除常规外周血检查和骨髓细胞形态分类外,本院患者采用了流式细胞术(FCM)分析T细胞受体β链V区(TCR BV)24家族,CD3、CD4、CD8、TCRαβ、TCRγδ等表达;RT-PCR扩增做TCR基因谱型图,分析异常细胞的克隆性;同时首次把西罗莫司(sirolimus)用于常规治疗无效的患者。结果表明,本院和文献中患者除外周血淋巴细胞绝对值高外,欧美患者以粒细胞缺乏为主,国内患者以纯红细胞再生障碍为主要表现。本院2例患者的大颗粒淋巴细胞辨别困难;FCM检测发现,淋巴细胞中以CD3+CD8+细胞为主,TCR BV呈单克隆分布;逆转录PCR扩增TCR BV 24基因家族与FCM结果一致;用西罗莫司(首剂6 mg口服,维持剂量2 mg/d)治疗1周后,血红蛋白、网织红细胞升高明显。结论:FCM检测特异性TCR BV单克隆淋巴细胞有利于LGLL确诊。西罗莫司可试用于LGLL患者治疗。This study was aimed to investigate the immunogenetic diagnosis of large granular lymphocytic leukemia(LGLL) and therapeutic efficacy of sirolimus,and to analysis 256 cases of LGLL reported at home and abroad within 2000-2010.Besides the routine examination of peripheral blood and classification of bone marrow cell morphology,the expression of T cell receptor variable region of β-chain(TCR BV),CD3,CD4 and CD8,as well as TCRαβ,TCRγδ were detected by flow cytometry;the RT-PCR was used to amplify and determine the TCR gene spectrotypes,and to analyzse the clonality of abnormal cells.Sirolimus was first given to patients who did not gain efficacy from common agents.The results showed that lymphocytosis happened in all LGLL patients,but patients from West countries always displayed neutropenia while Chinese patients always displayed anemia.In 2 out of 4 patients from our hospital,the large granular lymphocytes(LGL) were difficult to be distinguished.In all 4 patients,almost all lymphocytes were CD3+,CD8+,and TCRα/β+.TCR BV 24 gene family clones showed monoclonal TRBV 23,TRBV 20,TRBV 13.6,and TRBV 13.6,respectively.FCM results were consistent with those of RT-PCR.When 4 patients had been given sirolimus(6 mg first dose,2 mg once a day) for about 1 week,hemoglobin level and reticulocyte count increased significantly without any serious side effects.It is concluded that the detection of specific lymphocyte monoclonal TCR BV 24 gene family by FCM contributes to the diagnosis of LGLL.Sirolimus is an effective agent without serious side effect for LGLL patients,especially for patients who cannot tolerate common drugs.

关 键 词：大颗粒T淋巴细胞白血病 免疫基因诊断 西罗莫司 

分 类 号：R733.1[医药卫生—肿瘤] R733.7[医药卫生—临床医学]