Selective elimination of leukemic CD34<SUP>+</SUP> progenitor cells by cytotoxic T lymphocytes specific for WT1

作     者：Gao, LQ Bellantuono, I Elsässer, A Marley, SB Gordon, MY Goldman, JM Stauss, HJ 

作者机构：Hammersmith Hosp Imperial Sch Med Dept Immunol London England Hammersmith Hosp Imperial Sch Med Dept Hematol London England 

出 版 物：《BLOOD》 (血液)

年 卷 期：2000年第95卷第7期

页      面：2198-2203页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

主　　题：抗原/免疫学 抗原 CD34/分析 印迹法 蛋白质 骨髓净化/方法 DNA结合蛋白质类/分析 DNA结合蛋白质类/免疫学 基因 肾母细胞瘤 造血干细胞/化学 造血干细胞/免疫学 造血干细胞/病理学 T淋巴细胞 细胞毒性/免疫学 转录因子/分析 转录因子/免疫学 肿瘤细胞 培养的 WT1蛋白质类 成年人 儿童 人类 男(雄)性 

摘      要：Hematologic malignancies such as acute and chronic myeloid leukemia are characterized by the malignant transformation of immature CD34(+) progenitor cells. Transformation is associated with elevated expression of the Wilm s tumor gene encoded transcription factor (WT1), Here we demonstrate that WT1 can serve as a target for cytotoxic T lymphocytes (CTL) with exquisite specificity for leukemic progenitor cells. HLA-A0201-restricted CTL specific for WT1 kill leukemia cell lines and inhibit colony formation by transformed CD34(+) progenitor cells isolated from patients with chronic myeloid leukemia (CML), whereas colony formation by normal CD34(+) progenitor cells is unaffected. Thus, the tissue-specific transcription factor WT1 is an ideal target for CTL-mediated purging of leukemic progenitor cells in vitro and for antigen-specific therapy of leukemia and other WT1-expressing malignancies in vivo. (Blood. 2000;95:2198-2203) (C) 2000 by The American Society of Hematology.