[Infection stress and a driver mutation interact to promote transformation to hematological malignancies].

Goro Sashida
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引用次数: 0

Abstract

Myelodysplastic syndrome (MDS) is a refractory cancer that arises from hematopoietic stem cells and predominantly affects elderly adults. In addition to driver gene mutations, which are also found in clonal hematopoiesis in healthy elderly people, systemic inflammation caused by infection or collagen disease has long been known as an extracellular factor in the pathogenesis of MDS. Wild-type HSCs have an "innate immune memory" that functions in response to infection and inflammatory stress, and my colleagues and I used an infection stress model to demonstrate that the innate immune response by the TLR-TRIF-PLK-ELF1 pathway is similarly critical in impairment of hematopoiesis and dysregulation of chromatin in MDS stem cells. This revealed that not only are MDS stem cells expanded by the TRAF6-NF-kB pathway, the innate immune response is also involved in generating MDS stem cells. In this review, I will present research findings related to "innate immune memory," one of the pathogenic mechanisms of blood cancer, and discuss future directions for basic pathological research and potential therapeutic development.

[感染压力和驱动突变相互作用,促进向血液恶性肿瘤的转化]。
骨髓增生异常综合征(MDS)是一种由造血干细胞引起的难治性癌症,主要影响老年人。除了在健康老年人的克隆性造血中也发现的驱动基因突变外,感染或胶原病引起的全身炎症早已被认为是MDS发病机制中的细胞外因素。野生型造血干细胞具有 "先天性免疫记忆",可对感染和炎症应激做出反应。我和我的同事利用感染应激模型证明,TLR-TRIF-PLK-ELF1途径的先天性免疫反应同样是MDS干细胞造血功能受损和染色质失调的关键。这揭示了MDS干细胞不仅通过TRAF6-NF-kB途径扩增,先天性免疫反应也参与了MDS干细胞的生成。在这篇综述中,我将介绍与血癌致病机制之一的 "先天免疫记忆 "有关的研究成果,并讨论基础病理研究和潜在治疗开发的未来方向。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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