Aging-elevated inflammation promotes DNMT3A R878H-driven clonal hematopoiesis

作     者：Min Liao Ruiqing Chen Yang Yang Hanqing He Liqian Xu Yuxuan Jiang Zhenxing Guo Wei He Hong Jiang Jianwei Wang Min Liao;Ruiqing Chen;Yang Yang;Hanqing He;Liqian Xu;Yuxuan Jiang;Zhenxing Guo;Wei He;Hong Jiang;Jianwei Wang

作者机构：School of Pharmaceutical SciencesTsinghua UniversityBeijing 100084China Kidney Disease Centerthe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310003China Department of Hematology/OncologyFirst Hospital of Tsinghua UniversityBeijing 100016China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2022年第12卷第2期

页      面：678-691页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：the Beijing Advanced Innovation Center for Structural Biology and the Tsinghua-Peking Center for Life Sciences for facility and financial support supported by grant numbers 2018YFA0800200,2017YFA0104000,91849106,Z200022,Z181100001818005 and 81870118 to Jianwei Wang from the National Key R&D Program of China or the Beijing Municipal Science&Technology Commission and the National Natural Science Foundation of China 

主　　题：Aging Inflammation DNMT3A R882H Clonal hematopoiesis Hematopoietic stem cells Necroptosis TNFα 

摘      要：Aging-elevated DNMT3A R882H-driven clonal hematopoiesis(CH)is a risk factor for myeloid malignancies remission and overall *** some studies were conducted to investigate this phenomenon,the exact mechanism is still under *** this study,we observed that DNMT3 A R878 H bone marrow cells(human allele:DNMT3 A R882 H)displayed enhanced reconstitution capacity in aged bone marrow milieu and upon inflammatory ***3 A R878 H protects hematopoietic stem and progenitor cells from the damage induced by chronic inflammation,especially TNFa ***,we identified that RIPK1-RIPK3-MLKL-mediated necroptosis signaling was compromised in R878 H cells in response to proliferation stress and TNFa ***,we elucidated the molecular mechanism driving DNMT3 A R878 H-based clonal hematopoiesis,which raises clinical value for treating DNMT3 A R882 H-driven clonal hematopoiesis and myeloid malignancies with aging.