c-MPL 是一种候选表面标志物，赋予白血病干细胞自我更新、静止、化疗耐药和白血病起始潜能,STEM CELLS

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c-MPL 是一种候选表面标志物，赋予白血病干细胞自我更新、静止、化疗耐药和白血病起始潜能
STEM CELLS ( IF 4.0 ) Pub Date : 2018-09-05 , DOI: 10.1002/stem.2897
Huan Li ₁ , Na Zhao ₁ , Yihui Li ₁ , Haiyan Xing ₁ , Shuying Chen ₁ , Yingxi Xu ₁ , Kejing Tang ₁ , Zheng Tian ₁ , Min Wang ₁ , Qing Rao ₁ , Jianxiang Wang ₁

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急性髓性白血病 (AML) 由称为白血病干细胞 (LSC) 的独特的小白血病细胞亚群引发和维持。自我更新、静止和化疗耐药是 LSC 的关键干性特性，这对于传统疗法的临床反应不佳至关重要。识别 LSC 表面标志物和靶向 LSCs 对于开发潜在疗法很重要。在这项研究中，在 AML-ETO9a (AE9a) 白血病小鼠中应用化学疗法导致了被鉴定为 Lin-c-Kit+c-MPL+ 的化学耐药细胞群的富集。此外，Lin-c-Kit+ 白血病细胞中的这种 c-MPL 阳性细胞群包括高百分比的处于静止状态的细胞，集落形成能力增强，归巢效率提高。连续移植表明，Lin-c-Kit+c-MPL+ 细胞显示出显着高的白血病起始潜力。此外，已经证明在 AML 患者中，c-MPL 在大多数 CD34+ 白血病细胞上表达，并且 CD34+ 白血病细胞中 c-MPL+ 细胞的比例与预后不良有关。最后，当与化疗药物联合使用时，c-MPL 抑制剂 AMM2 可显着提高 AE9a 白血病小鼠的存活率。这些结果表明，c-MPL 是一种候选的 LSC 表面标志物，可以作为消除 LSC 的治疗靶点。干细胞 2018；36：1685–1696 c-MPL 在大多数 CD34+ 白血病细胞上表达，CD34+ 白血病细胞中 c-MPL+ 细胞的比例与预后不良有关。最后，当与化疗药物联合使用时，c-MPL 抑制剂 AMM2 可显着提高 AE9a 白血病小鼠的存活率。这些结果表明，c-MPL 是一种候选的 LSC 表面标志物，可以作为消除 LSC 的治疗靶点。干细胞 2018；36：1685–1696 c-MPL 在大多数 CD34+ 白血病细胞上表达，CD34+ 白血病细胞中 c-MPL+ 细胞的比例与预后不良有关。最后，当与化疗药物联合使用时，c-MPL 抑制剂 AMM2 可显着提高 AE9a 白血病小鼠的存活率。这些结果表明，c-MPL 是一种候选的 LSC 表面标志物，可以作为消除 LSC 的治疗靶点。干细胞 2018；36：1685–1696

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c-MPL is a candidate surface marker and confers self-renewal, quiescence, chemotherapy resistance and leukemia initiation potential in leukemia stem cells

Acute myeloid leukemia (AML) is initiated and maintained by a unique, small subset of leukemia cells known as leukemia stem cells (LSCs). Self‐renewal, quiescence, and chemotherapy resistance are key stemness properties of LSCs that are essential for poor clinical responses to conventional therapies. Identifying LSC surface markers and targeting LSCs are important for the development of potential therapies. In this study, application of chemotherapy treatment in AML‐ETO9a (AE9a) leukemia mice led to the enrichment of a chemotherapy‐resistant cell population identified as Lin−c‐Kit+c‐MPL+. In addition, this c‐MPL‐positive cell population within Lin−c‐Kit+ leukemia cells included a high percentage of cells in a quiescent state, enhanced colony formation ability, and increased homing efficiency. Serial transplantation demonstrated that Lin−c‐Kit+c‐MPL+ cells displayed a significantly high potential for leukemia initiation. Furthermore, it was demonstrated that in AML patients, c‐MPL was expressed on the majority of CD34+ leukemia cells and that the proportion of c‐MPL+ cells in CD34+ leukemia cells is associated with poor prognosis. Finally, AMM2, an inhibitor of c‐MPL, was shown to significantly enhance the survival of AE9a leukemia mice when combined with chemotherapeutic agent. These results indicate that c‐MPL is a candidate LSC surface marker that may serve as a therapeutic target for the elimination of LSCs. Stem Cells 2018;36:1685–1696

更新日期：2018-09-05

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