Department of Medicine and Biosystemic Sciences, Kyushu University Graduate School of Medicine, Fukuoka, Japan.
Ann N Y Acad Sci. 2012 Aug;1266:118-23. doi: 10.1111/j.1749-6632.2012.06550.x.
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 in most 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.
急性髓系白血病（AML）起源于自我更新的白血病干细胞（LSCs），这是 AML 的一个终极治疗靶点。最近的研究表明，许多 AML LSC 特异性表面抗原可能是此类候选物。T 细胞免疫球蛋白黏蛋白-3（TIM-3）在除急性早幼粒细胞白血病以外的大多数 AML 类型的 LSCs 上表达，但不在正常造血干细胞（HSCs）上表达。在用人 AML LSCs 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 IgG2a 抗体可在体内根除 AML LSCs，但不影响正常的人类造血。因此，TIM-3 是根除 AML LSCs 的有前途的靶标之一。
