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Blood：在急性髓系白血病中，NPM1c如何影响FLT3-D835Y的定位及信号？

2019-06-22 MedSci MedSci原创

急性髓系白血病NPM1cFLT3TKD
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中心点：两种常见的AML突变，NPM1c和FLT3-TKD，可协同诱导小鼠快速发病。在机制上，NPM1c会改变FLT3-TKD的定位并改变其信号特性，这可能有助于治疗干预。摘要：在急性髓系白血病(AML)中，FLT3和NPM1的激活突变是最常见的变异，而且常同时发生。NPM1的突变状态对于携带FLT3酪氨酸激酶结构域(TKD)点突变的患者具有很强的预后相关性，但其生物学机制尚不明确。近期Alina

中心点：

两种常见的AML突变，NPM1c和FLT3-TKD，可协同诱导小鼠快速发病。

在机制上，NPM1c会改变FLT3-TKD的定位并改变其信号特性，这可能有助于治疗干预。

摘要：

在急性髓系白血病(AML)中，FLT3和NPM1的激活突变是最常见的变异，而且常同时发生。NPM1的突变状态对于携带FLT3酪氨酸激酶结构域(TKD)点突变的患者具有很强的预后相关性，但其生物学机制尚不明确。

近期Alina Rudorf等人发现NPM1c与FLT3-TKD具有协同效应。虽然FLT3-TKD的表达不足以诱导小鼠发病，但与NPM1c共同表达时可导致小鼠迅速发生侵袭性骨髓增生性疾病，潜伏期仅31.5天。

研究人员发现，仅在突变型NPM1c存在的情况下，FLT3-TKD才可激活下游效应分子STAT5。此外，NPM1c会改变FLT3-TKD从细胞表面到内质网的细胞定位，进而可能导致STAT5异常激活。更重要的是，STAT5异常激活不仅发生于原发性小鼠细胞中，在携带FLT3-TKD和NPM1c突变的AML患者中也有发生。

总而言之，本研究揭示了一种新的机制，即NPM1c导致FLT3-TKD异常定位和改变其信号转导能力的机制。

原始出处：

Alina Rudorf， et al. NPM1c alters FLT3-D835Y localization and signaling in acute myeloid leukemia. Blood 2019 ：blood.2018883140； doi： https：//doi.org/10.1182/blood.2018883140

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    2020-03-10 医者仁心

    #PM1#

    0

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    2019-12-09 hb2008ye

    #髓系白血病#

    0

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    2019-10-30 rebeccajiejie

    #NPM1c#

    0

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    2019-06-24 fengyi816

    #FLT3#

    0

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    2019-06-24 zhaohui6736

    #NPM1#

    0

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