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Therapeutic targeting of the inflammasome in myeloid malignancies
Blood Cancer Journal ( IF 12.9 ) Pub Date : 2021-09-14 , DOI: 10.1038/s41408-021-00547-8
Samarpana Chakraborty 1, 2 , Lauren C Shapiro 1, 2, 3 , Sofia de Oliveira 2, 4 , Bianca Rivera-Pena 1, 2 , Amit Verma 1, 2, 3 , Aditi Shastri 1, 2, 3
Affiliation  

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.



中文翻译:

骨髓恶性肿瘤中炎症小体的治疗靶向

尽管遗传扰动和突变对髓系恶性肿瘤的发展很重要,但炎症微环境的影响是致癌的关键调节剂。通过各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) 和急性髓性白血病 (AML) 的重要驱动因素。通过 TLR4/NLR 信号级联激活炎性体通路的 DAMP 或警报素导致造血干细胞和祖细胞 (HSPC) 裂解细胞死亡、无效的造血和 β-连环蛋白诱导的癌细胞增殖,导致MDS/AML 表型的发展。它还与其他髓系恶性肿瘤有关,并参与相关血细胞减少的发病机制。正在进行的研究表明,炎性体介质与免疫调节剂和转录因子的相互作用在骨髓疾病的发展和可能的治疗抵抗中具有重要作用。本综述讨论了炎症小体和免疫通路在髓系恶性肿瘤,特别是 MDS/AML 中的作用和重要性,以更好地了解疾病的病理生理学并破译治疗干预的范围。

更新日期:2021-09-14
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