Blood:TP53突变对MDS和继发性AML预后的影响

2020-08-07 MedSci原创 MedSci原创

TP53突变型MDS和sAML的选定检查点分子的调控发生改变;靶向TP53突变患者循环中的mir-34a-MYC-PDL1代表了一种新的疗法。

体细胞基因突变是骨髓增生异常综合征(MDS)和继发性急性髓细胞白血病(SAML)患者预后的关键决定因素。特别是TP53突变,代表了一种不同的分子队列,携带TP53突变的患者的预后往往都很差。然后,这些不良结果潜在的确切致病机制尚未阐明。

在本研究中,Sallman等描述了TP53突变和野生型MDS和SAML患者免疫微环境中的恶性克隆的免疫学特征及其变化。

值得注意的是,PD-L1在TP53突变型患者造血干细胞中的表达显著增加,这与MYC上调和MYC的负调控因子miR-34a(p53转录靶标)显著下调有关。此外,TP53突变型患者的骨髓中浸润的OX40+细胞毒性T细胞和辅助T细胞数量显著减少,与ICOS+和4-1BB+NK细胞减少一样。

在TP53突变型病例中,高免疫抑制调节性T细胞(如ICOS High/PD-1neg)和MDSCs(PD-1low)扩增。最后,较高比例的骨髓浸润ICOS High/PD-1neg Tregs是总体生存率的一个非常显著的独立预测因子。

综上所述,本研究表明,TP53突变型MDS和SAML的微环境具有免疫特权和回避表型,这可能是患者不良预后的主要驱动因素,并提出免疫调节治疗策略可能为这一类亚群患者提供好处。

原始出处:

David A. Sallman,et al. TP53 mutations in myelodysplastic syndromes and secondary AML confer an immunosuppressive phenotype. Blood. July 30,2020.

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    2020-08-13 d830372
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    2021-04-18 ms1000000998771471

    学习了

    0

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    2021-03-28 xzw113
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    2021-04-15 feifers
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    2020-08-09 zhishijing
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    2020-08-09 zblhy
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    2020-08-08 ms3000000449926787

    挺好的

    0

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