TIM-3 as a therapeutic target for malignant stem cells in acute myelogenous leukemia
TIM-3 as a therapeutic target for malignant stem cells in acute myelogenous leukemia
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DOI：
10.1111/j.1749-6632.2012.06550.x
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发表时间：
2012-01-01
期刊：
影响因子：
--
通讯作者：
Akashi, Koichi
中科院分区：
文献类型：
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作者：
Kikushige, Yoshikane;Akashi, Koichi
急性髓性白血病（AML）起源于自我更新的白血病干细胞（LSC），这是AML的最终治疗靶点。最近的研究表明，许多AML LSC特异性表面抗原可能是这样的候选者。T细胞免疫球蛋白粘蛋白-3（TIM-3）在大多数类型的AML中的LSC上表达，但在正常造血干细胞（HSC）上不表达，急性早幼粒细胞白血病除外。在用人AML LSC或人造血干细胞重建的小鼠模型中，具有补体依赖性和抗体依赖性细胞毒性活性的人TIM-3小鼠IgG 2a抗体在体内根除AML LSC，但不影响正常人造血。因此，TIM-3是根除AML LSC的有希望的靶标之一。
Acute myeloid leukemia (AML) originates from self-renewing leukemic stem cells (LSCs), an ultimate therapeutic target for AML. Recent studies have shown that many AML LSC-specific surface antigens could be such candidates. T cell immunoglobulin mucin-3 (TIM-3) is expressed on LSCs inmost types of AML, except for acute promyelocytic leukemia, but not on normal hematopoietic stem cells (HSCs). In mouse models reconstituted with human AML LSCs or human hematopoietic stem cells, a human TIM-3 mouse IgG2a antibody with complement-dependent and antibody-dependent cellular cytotoxic activities eradicates AML LSCs in vivo but does not affect normal human hematopoiesis. Thus, TIM-3 is one of the promising targets to eradicate AML LSCs.