文章：

髓系恶性肿瘤中炎症小体的治疗性靶向

Therapeutic targeting of the inflammasome in myeloid malignancies

原文发布日期：2021-09-14

DOI: 10.1038/s41408-021-00547-8

类型: Review Article

开放获取: 是

英文摘要：

Even though genetic perturbations and mutations are important for the development of myeloid malignancies, the effects of an inflammatory microenvironment are a critical modulator of carcinogenesis. Activation of the innate immune system through various ligands and signaling pathways is an important driver of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). The DAMPs, or alarmins, which activate the inflammasome pathway via the TLR4/NLR signaling cascade causes the lytic cell death of hematopoietic stem and progenitor cells (HSPCs), ineffective hematopoiesis, and β-catenin-induced proliferation of cancer cells, leading to the development of MDS/AML phenotype. It is also associated with other myeloid malignancies and involved in the pathogenesis of associated cytopenias. Ongoing research suggests the interplay of inflammasome mediators with immune modulators and transcription factors to have a significant role in the development of myeloid diseases, and possibly therapy resistance. This review discusses the role and importance of inflammasomes and immune pathways in myeloid malignancies, particularly MDS/AML, to better understand the disease pathophysiology and decipher the scope of therapeutic interventions.
 

摘要翻译： 

尽管遗传扰动和突变对髓系恶性肿瘤的发展至关重要，但炎症微环境的影响是致癌过程的关键调节因素。通过多种配体和信号通路激活先天免疫系统，是骨髓增生异常综合征（MDS）和急性髓系白血病（AML）的重要驱动因素。损伤相关分子模式（即警报素）通过TLR4/NLR信号级联激活炎症小体通路，导致造血干细胞和祖细胞发生溶解性死亡、无效造血以及β-连环蛋白驱动的癌细胞增殖，最终形成MDS/AML表型。该机制也与其他髓系恶性肿瘤相关，并参与相关血细胞减少症的发病过程。现有研究表明，炎症小体介质与免疫调节因子、转录因子之间的相互作用在髓系疾病发展及潜在治疗耐药性中具有重要作用。本综述探讨了炎症小体及免疫通路在髓系恶性肿瘤（特别是MDS/AML）中的作用与重要性，以深化对疾病病理生理学的理解，并探索治疗干预的空间。

原文链接：

Therapeutic targeting of the inflammasome in myeloid malignancies