TIM-3 as a novel therapeutic target for eradicating acute myelogenous leukemia stem cells
TIM-3 as a novel therapeutic target for eradicating acute myelogenous leukemia stem cells
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DOI：
10.1007/s12185-013-1433-6
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发表时间：
2013-12-01
影响因子：
2.1
通讯作者：
Miyamoto, Toshihiro
中科院分区：
文献类型：
--
作者：
Kikushige, Yoshikane;Miyamoto, Toshihiro
急性髓性白血病（AML）起源于自我更新的白血病干细胞（LSC），其代表AML的最终治疗靶点。最近的研究已经确定了几种AML LSC特异性表面抗原作为治疗分子的候选靶标。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，但急性早幼粒细胞白血病除外，但在正常造血干细胞（HSC）上不表达。在用人AML LSC或HSC重建的异种移植物模型中，具有细胞毒性活性的抗人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的有希望的治疗靶标。
Acute myelogenous leukemia (AML) originates from self-renewing leukemic stem cells (LSCs), which represent the ultimate therapeutic target for AML. Recent studies have identified several AML LSC-specific surface antigens as candidate targets of therapeutic molecules. T cell immunoglobulin mucin-3 (TIM-3) is expressed on LSCs in most types of AML, with the exception of acute promyelocytic leukemia, but not on normal hematopoietic stem cells (HSCs). In xenograft models reconstituted with human AML LSCs or HSCs, an anti-human TIM-3 mouse IgG2a antibody with cytotoxic activities eradicates AML LSCs in vivo, but does not affect normal human hematopoiesis. Thus, TIM-3 is a promising therapeutic target for the eradication of AML LSCs.