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关于炎症小体在白血病中的作用的研究进展:我们了解多少?

Insights Regarding the Role of Inflammasomes in Leukemia: What Do We Know?

机构信息

Programa de Pós-Graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas (UFAM), Manaus, AM, Brazil.

Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, AM, Brazil.

出版信息

J Immunol Res. 2023 Aug 4;2023:5584492. doi: 10.1155/2023/5584492. eCollection 2023.

Abstract

Inflammation is a physiological mechanism of the immune response and has an important role in maintaining the hematopoietic cell niche in the bone marrow. During this process, the participation of molecules produced by innate immunity cells in response to a variety of pathogen-associated molecular patterns and damage-associated molecular patterns is observed. However, chronic inflammation is intrinsically associated with leukemogenesis, as it induces DNA damage in hematopoietic stem cells and contributes to the creation of the preleukemic clone. Several factors influence the malignant transformation within the hematopoietic microenvironment, with inflammasomes having a crucial role in this process, in addition to acting in the regulation of hematopoiesis and its homeostasis. Inflammasomes are intracellular multimeric complexes responsible for the maturation and secretion of the proinflammatory cytokines interleukin-1 and interleukin-18 and the cell death process via pyroptosis. Therefore, dysregulation of the activation of these complexes may be a factor in triggering several diseases, including leukemias, and this has been the subject of several studies in the area. In this review, we summarized the current knowledge on the relationship between inflammation and leukemogenesis, in particular, the role of inflammasomes in different types of leukemias, and we describe the potential therapeutic targets directed at inflammasomes in the leukemic context.

摘要

炎症是免疫反应的一种生理机制,在维持骨髓造血细胞龛中起着重要作用。在此过程中,观察到固有免疫细胞产生的分子对各种病原体相关分子模式和损伤相关分子模式的反应参与其中。然而,慢性炎症本质上与白血病发生有关,因为它会导致造血干细胞中的 DNA 损伤,并有助于前白血病克隆的形成。几种因素影响造血微环境中的恶性转化,其中炎性小体在这个过程中起着关键作用,除了在调节造血及其稳态方面发挥作用。炎性小体是负责细胞因子白细胞介素-1 和白细胞介素-18 的成熟和分泌以及通过细胞焦亡导致细胞死亡的细胞内多聚体复合物。因此,这些复合物的激活失调可能是引发包括白血病在内的多种疾病的一个因素,这也是该领域的一些研究的主题。在这篇综述中,我们总结了炎症与白血病发生之间的关系的现有知识,特别是炎性小体在不同类型白血病中的作用,并描述了针对白血病背景下炎性小体的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dee/10421713/deb22058b3ef/JIR2023-5584492.001.jpg

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