Germline variants in acquired aplastic anemia: current knowledge and future perspectives
Peicheng Wang,
Wanzhi Jiang,
Tianyi Lai,
Qi Liu,
Yingying Shen,
Baodong Ye,
Dijiong Wu
Affiliations
Peicheng Wang
Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China; The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang
Wanzhi Jiang
Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China; The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang
Tianyi Lai
Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China; The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang
Qi Liu
Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China; The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang
Yingying Shen
Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China; The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China; National Traditional Chinese Medicine Clinical Research Base (Hematology), Hangzhou, Zhejiang
Baodong Ye
Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China; The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China; National Traditional Chinese Medicine Clinical Research Base (Hematology), Hangzhou, Zhejiang
Dijiong Wu
Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China; The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China; National Traditional Chinese Medicine Clinical Research Base (Hematology), Hangzhou, Zhejiang, China; Department of Oncology and Hematology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine affiliated to Zhejiang Chinese Medicine University, Wenzhou, Zhejiang
Aplastic anemia (AA) is a disease characterized by hematopoiesis failure, bone marrow aplasia, and pancytopenia. It can be inherited or acquired. Although acquired AA is believed to be immune-mediated and random, new evidence suggests an underlying genetic predisposition. Besides confirmed genomic mutations that contribute to inherited AA (such as pathogenic mutations of TERT and TERC), germline variants, often in heterozygous states, also play an unignorable role in the onset and progression of acquired AA. These variants, associated with inherited bone marrow failure syndromes (IBMFS) and inborn errors of immunity (IEI), contribute to the disease possibly through mechanisms including gene homeostasis, DNA repair, and immune injury. This article explores the nuanced association between acquired AA and germline variants, detailed the clinical significance of germline variants in diagnosing and clinical management of this condition. More works are encouraged to better understand the role of immunogenic pathogenic variants and whether somatic mutation participate as secondary “hit” in the development of bone marrow failure.
