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在急性髓性白血病中,三种AKT异型的不同预后值

Eulalie Corre¹, Cécile Soum¹, Romain Pfeifer¹

¹Centre de Recherches en Cancérologie de Toulouse (CRCT), INSERM UMR-1037, CNRS UMR-5071, Université de Toulouse, Toulouse, France.

Scientific reports

|March 26, 2024

概括

这项研究表明,AKT3和AKT1在急性髓性白血病 (AML) 中具有相反的作用. 高的AKT3预示着生存率较低,而高的AKT1则表明AML患者的治疗结果更好.

科学领域:

分子生物学分子生物学
在瘤学瘤学.
血液学血液学血液学

背景情况:

在急性髓性白血病 (AML) 发病过程中,PI3K-AKT-mTOR通路至关重要.
人体存在三种AKT异型 (AKT1,AKT2,AKT3),但它们在AML中的具体作用尚不清楚.

研究的目的:

调查AKT异型在正常骨髓细胞分化和AML中的不同作用和预后值.
为了确定特定的AKT异型是否在AML中占主导地位.

主要方法:

在正常骨髓分化过程中分析AKT异型表达.
在AML患者样本中评估AKT异型表达.
AKT表达水平与遗传变异和患者生存结果的相关性.

主要成果:

在正常分化过程中,AKT3优先表达在造血干细胞中,而在粒细胞/单细胞成熟过程中,AKT1增加.
在AML中,AKT3的表达有很大差异,在成熟/单细胞白血病中高.
低AKT3表达与有利的基因变异相关 (NPM1,RUNX1-RUNX1T1),而高AKT3与不利的突变相关 (RUNX1,SRSF2,U2AF1,SF3B1,ASXL1,BCOR) 和生存率差.
相反,高AKT1表达预示着AML患者的更好的治疗结果.

结论:

在AML中,AKT3和AKT1具有不同的和相反的预后值.
AKT3表达水平是AML患者生存的强有力的预测指标.

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PI3K/mTOR/AKT Signaling Pathway

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The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...