Selective elimination of leukemic CD34+ progenitor cells by cytotoxic T lymphocytes specific for WT1
Selective elimination of leukemic CD34+ progenitor cells by cytotoxic T lymphocytes specific for WT1
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DOI：
10.1182/blood.v95.7.2198.007k38_2198_2203
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发表时间：
2000-04-01
期刊：
影响因子：
20.3
通讯作者：
Stauss, HJ
中科院分区：
文献类型：
--
作者：
Gao, LQ;Bellantuono, I;Stauss, HJ
血液恶性肿瘤如急性和慢性髓性白血病的特征是未成熟的CD 34（+）祖细胞的恶性转化。转化与Wilm's肿瘤基因编码的转录因子（WT 1）的表达升高相关。在此，我们证明WT 1可以作为细胞毒性T淋巴细胞（CTL）的靶点，对白血病祖细胞具有精确的特异性。WT 1特异性的HLA-A0201限制性CTL杀伤白血病细胞系，并抑制从慢性髓性白血病（CML）患者分离的转化的CD 34（+）祖细胞的集落形成，而正常CD 34（+）祖细胞的集落形成不受影响。因此，组织特异性转录因子WT 1是体外CTL介导的白血病祖细胞净化和体内白血病和其他表达WT 1的恶性肿瘤的抗原特异性治疗的理想靶点。（血。2000;95：2198-2203）（C）2000由美国血液学学会。
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.