急性髓系白血病患者外周血T细胞TCR Vβ亚家族表达及克隆性增殖分析  

Expression and Clonal Proliferation of TCR Vβ Subfamilies of Peripheral T-cells in Acute Myeloid Leukemia Patients

作　　者：毛平[1] 罗畅如[1] 张玉平[1] 王彩霞[1] 许艳丽[1] 应逸[1] 杜庆华[1] 谢健晋[1] 

机构地区：[1]广州医学院附属广州市第一人民医院血液内科,广东广州510180

出　　处：《中国实验血液学杂志》2009年第2期431-436,共6页Journal of Experimental Hematology

基　　金：国家自然科学基金(编号30471644);广东省自然科学基金重点项目(编号06112013)

摘　　要：本研究探讨AML患者在初发、治疗缓解后、复发等不同疾病状态下外周血T细胞TCRVβ亚家族表达及T细胞克隆性增殖的情况,分析不同白血病细胞负荷对患者外周血T淋巴细胞数量及功能,尤其是对抗白血病功能的影响。应用RT-PCR扩增11例AML白血病患者不同疾病状态下及3名正常供者外周血的TCRBV24个家族的基因序列,通过基因扫描(genescan)的方法判断TCRBV家族的克隆表达、CDR3克隆性质,比较不同疾病状态下白血病患者外周血T细胞的Vβ亚家族的应用、克隆性增殖、T细胞的复杂性以及T细胞免疫表型的变化。结果表明:11例AML白血病患者初诊时外周血T细胞均表达部分TCRVβ亚家族,经体外诱导后TCRVβ亚家族表达增加;完全缓解期患者外周血T细胞TCRVβ亚家族数量明显增多,但未达到完全正常;4例患者在复发时TCRVβ亚家族表达数量明显下降;11例患者中有9例在初诊时外周血有1至2个TCRVβ亚家族T细胞克隆性增殖,缓解期克隆性增殖的Vβ亚家族T细胞有增加趋势,在多数病例观察到部分Vβ亚家族T细胞在初发、缓解、体外诱导扩增以及复发时仍维持克隆性增殖状态;AML白血病患者初发及复发时T细胞CDR3复杂性明显降低,呈偏态分布,而疾病缓解时T细胞复杂性有所改善。结论:AML白血病患者外周血T细胞TCRVβ亚家族呈限制性表达;在大多数病例中无论是疾病初发抑或缓解及体外诱导、甚至在疾病复发时均可观察到克隆性T细胞的存在;在部分病例中某些Vβ亚家族在上述不同疾病状态下始终维持克隆性增殖状态,部分Vβ亚家族的克隆性增殖同白血病细胞的存在相关;在疾病状态下,AML白血病患者外周血T细胞的复杂性有所降低,而疾病缓解后可部分恢复。This study was purposed to investigate the expression and clonal proliferation of receptor （TCR） Vβ subfamilies of the T-cells in acute leukemic patients at different disease status （ onset, complete remission or relapse ） and to analyze the influence of the leukemic cell load on anti-leukemic effect of peripheral T-lymphocytes of the patients. Gene sequences of peripheral TCR Vβ 24 families from 11 leukemic patients and 3 normal donors were expanded by RT-PCR. Genescan technique was applied to evaluate clonal expression of the TCRVβ subfamilies, clonal characteristics of the CDR3 from peripheral blood of AML patients at different disease status. The application, clonal proliferation, cellular complexity of T-cells, and the variation of immunotypes of T-cells were compared. The results indicated that the lower and partial distribution of TCR Vβ subfamily was found in all 11 patients when firstly diagnosed; the expression of TCR Vβ subfamilies after induction in vitro increased; obvious elevation of TCR Vβ subfamilies was observed in patients at complete remission although expression level was still lower than normal, whereas the significant descent of TCR Vβ subfamilies was detected in 4 relapsed patients. Only 1 - 2 clonal proleferation of TCR Vβ subfamilies existed in 9 out of 11 patients at initial diagnosis which increased at remission. The status of clonal proliferation of Vβ subfamily T-cells continued regardless of any different disease status in most patients. There was an obvious decrease of CDR3 complexity at initial diagnosis or relapse, while CDR3 complexity would be partially improved at remission. It is concluded that the restrict distribution and expression of TCR Vβ subfamilies were found in AML patients. Clonal proliferation of T- cells Vβ subfamily continuously exists regardless of any different disease status in most patients. Some Vβ subfamilies sustain clonal proliferation at different disease status. Some clonal proliferations of Vβ subfamilies are associated with the ef

关 键 词：急性髓系白血病 T淋巴细胞 VΒ亚家族 克隆性增殖 

分 类 号：R733.7[医药卫生—肿瘤]