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Blood：PRDM16s促进巨核-红系祖细胞转化为急性髓系白血病初始细胞

2019-07-06 MedSci MedSci原创

PRDM16s红系祖细胞急性髓系白血病初始细胞
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中心点：Prdm16将巨核细胞-红系祖细胞转化为髓系白血病干细胞Prdm16激活PU.1的表达是其诱导白血病发生的必经之路摘要：致癌突变赋予细胞无限增殖的能力，但致癌基因是否改变这些细胞的命运尚不清楚。Tianyuan Hu等人发现转录调控因子PRDM16s可通过将要形成血小板和红细胞的细胞转化成骨髓性白血病干细胞(LSCs)，从而导致致癌命运的转变。在正常情况下，巨核细胞红系祖细胞(MEPs)并

中心点：

Prdm16将巨核细胞-红系祖细胞转化为髓系白血病干细胞

Prdm16激活PU.1的表达是其诱导白血病发生的必经之路

摘要：

致癌突变赋予细胞无限增殖的能力，但致癌基因是否改变这些细胞的命运尚不清楚。

Tianyuan Hu等人发现转录调控因子PRDM16s可通过将要形成血小板和红细胞的细胞转化成骨髓性白血病干细胞(LSCs)，从而导致致癌命运的转变。在正常情况下，巨核细胞红系祖细胞(MEPs)并没有生成颗粒单核细胞的潜能，但Prdm16s在MEPs中表达时可通过将MEPs转化为LSCs而导致AML。

Prdm16s通过与超级增强子相互作用和激活髓系主要的调节因子(包括PU.1)阻断巨核细胞/红细胞潜能。通过CRISPR-dropout筛选发现，PU.1对Prdm16诱导的白血病至关重要。

在小鼠模型和人AML中，通过PRDM16重排去除PU1可以减缓白血病的发生，恢复白血病的巨核细胞/红细胞潜能。

总而言之，致癌基因PRDM16表达通过激活髓样基因调控网络将MEPs转化为LSC。

原始出处：

Tianyuan Hu， et al.PRDM16s transforms megakaryocyte-erythroid progenitors to acute myeloid leukemia-initiating cells.Blood 2019 ：blood.2018888255； doi： https：//doi.org/10.1182/blood.2018888255

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    2020-03-07 fangcong

    #髓系白血病#

    0

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    2020-02-11 江川靖瑶

    #PRDM16s#

    0

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    2019-07-08 12498636m52(暂无昵称)

    #祖细胞#

    0

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    2019-07-06 百草

    666

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