Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia.
Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia.
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Musashi（Msi）家族的RNA结合蛋白在干细胞区室和侵袭性肿瘤中表达，但在血液中尚未得到广泛研究。在此我们证明，Msi2是在造血干细胞（HSCs）中表达的主要形式，其敲低会导致体内造血干细胞植入减少和耗竭。在小鼠模型中过表达人MSI2会增加造血干细胞的细胞周期进程，并与慢性髓系白血病相关的BCR - ABL1癌蛋白协同诱导侵袭性白血病。MSI2在人髓系白血病细胞系中过表达，其缺失会导致增殖减少和凋亡增加。人髓系白血病中的表达水平与该病患者的生存率降低直接相关，从而将MSI2表达定义为一种新的预后标志物以及急性髓系白血病（AML）治疗的新靶点。
RNA-binding proteins of the Musashi (Msi) family are expressed in stem cell compartments and in aggressive tumors, but they have not yet been widely explored in the blood. Here we demonstrate that Msi2 is the predominant form expressed in hematopoietic stem cells (HSCs), and its knockdown leads to reduced engraftment and depletion of HSCs in vivo. Overexpression of human MSI2 in a mouse model increases HSC cell cycle progression and cooperates with the chronic myeloid leukemia–associated BCR-ABL1 oncoprotein to induce an aggressive leukemia. MSI2 is overexpressed in human myeloid leukemia cell lines, and its depletion leads to decreased proliferation and increased apoptosis. Expression levels in human myeloid leukemia directly correlate with decreased survival in patients with the disease, thereby defining MSI2 expression as a new prognostic marker and as a new target for therapy in acute myeloid leukemia (AML).