TIM-3 Is a Promising Target to Selectively Kill Acute Myeloid Leukemia Stem Cell

jiandong2001

1.说明：原文来源自 Cell Stem Cell，由干细胞之家新闻小组成员jiandong2001翻译（转帖请注明）
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2.翻译内容：急性髓细胞白血病（AML）起源于可自我更新的白血病干细胞（LSCs），这是AML治疗的最终靶点。本文中，作者证实细胞表面分子T细胞免疫球蛋白粘蛋白3（TIM-3）表达于除了急性早幼粒细胞白血病之外的所有AML中，在正常造血干细胞（HSCs）表面不表达。TIM-3阳性细胞，而非TIM-3阴性细胞，可在免疫缺陷小鼠体内重现人髓细胞白血病，这就提示TIM-3阳性细胞至少包含了绝大多数有功能的LSCs。作者制作了一种鼠抗人TIM-3 Ig2a抗体，这种抗体具有补体依赖于抗体的依赖的细胞毒活性，其对正常人造血干细胞无害，但可阻止移植宿主体内形成AML。此外，对形成AML移植物的小鼠给予该抗体治疗后，可显著减轻肿瘤负荷，并清除可在第二代宿主体内形成移植瘤的KSCs，这些结果提示TIM-3有望成为根除AML中LSCs的靶点之一。
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3.原文：Acute myeloid leukemia (AML) originates from selfrenewing leukemic stem cells (LSCs), an ultimate therapeutic target for AML. Here we identified T cell immunoglobulin mucin-3 (TIM-3) as a surface molecule expressed on LSCs in most types of AML except for acute promyelocytic leukemia, but not on normal hematopoietic stem cells (HSCs). TIM-3+ but not TIM-3 AML cells reconstituted human AML in immunodeficient mice, suggesting that the TIM-3+ population contains most, if not all, of functional LSCs. We established an anti-human TIM-3 mouse IgG2a antibody having complement-dependent and antibody-dependent cellular cytotoxic activities. This antibody did not harm reconstitution of normal human HSCs, but blocked engraftment of AML after xenotransplantation. Furthermore, when it is administered into mice grafted with human AML, this treatment dramatically diminished their leukemic burden and eliminated LSCs capable of reconstituting human AML in secondary recipients. These data suggest that TIM-3 is one of the promising targets to eradicate AML LSCs.
8 t( o& Z0 n8 c( B9 Q3 L. I& j4.原文附件已上传
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5.个人翻译，理解不准确的语句还望大家积极指出。
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) r; S# x' h/ I$ ?  A6.血液系统干细胞的研究一直走在前面，有很多值得借鉴的地方！本文的发现还是很值得期待的

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