Therapeutic targeting of the inflammasome in myeloid malignancies.
Therapeutic targeting of the inflammasome in myeloid malignancies.
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DOI：
10.1038/s41408-021-00547-8
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发表时间：
2021-09-14
影响因子：
12.8
通讯作者：
Shastri A
中科院分区：
文献类型：
--
作者：
Chakraborty S;Shapiro LC;de Oliveira S;Rivera-Pena B;Verma A;Shastri A
尽管遗传扰动和突变对于骨髓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因素。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) 和急性髓系白血病 (AML) 的重要驱动因素。 DAMP 或警报素通过 TLR4/NLR 信号级联激活炎症小体途径，导致造血干细胞和祖细胞 (HSPC) 裂解细胞死亡、无效造血和 β-连环蛋白诱导的癌细胞增殖，从而导致 MDS/AML 表型的发展。它还与其他骨髓恶性肿瘤相关，并参与相关血细胞减少症的发病机制。正在进行的研究表明，炎症小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中发挥着重要作用，并可能导致治疗耐药。本综述讨论了炎症小体和免疫途径在骨髓恶性肿瘤（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阐明治疗干预的范围。
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.
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DOI：
10.1056/nejmoa1409405
发表时间：
2014-12-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Genovese G;Kähler AK;Handsaker RE;Lindberg J;Rose SA;Bakhoum SF;Chambert K;Mick E;Neale BM;Fromer M;Purcell SM;Svantesson O;Landén M;Höglund M;Lehmann S;Gabriel SB;Moran JL;Lander ES;Sullivan PF;Sklar P;Grönberg H;Hultman CM;McCarroll SA
通讯作者：
McCarroll SA
影响因子：
16
作者：
Crispino, JD;Lodish, MB;Orkin, SH
通讯作者：
Orkin, SH
DOI：
10.1084/jem.20131141
发表时间：
2013-11-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Abdel-Wahab O;Gao J;Adli M;Dey A;Trimarchi T;Chung YR;Kuscu C;Hricik T;Ndiaye-Lobry D;Lafave LM;Koche R;Shih AH;Guryanova OA;Kim E;Li S;Pandey S;Shin JY;Telis L;Liu J;Bhatt PK;Monette S;Zhao X;Mason CE;Park CY;Bernstein BE;Aifantis I;Levine RL
通讯作者：
Levine RL
影响因子：
7.3
作者：
Alagha, Afnan;Zaikin, Alexey
通讯作者：
Zaikin, Alexey
影响因子：
4.2
作者：
Gummadi, Venkateshwar Rao;Boruah, Anima;Samajdar, Susanta
通讯作者：
Samajdar, Susanta