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Spermidine Related Autophagy Flux Deficiency is a Novel Pathogenesis of Aplastic Anemia

Jinqi Huang1,2*,Yuming Zhang1 , Juan Xia1 , Chen Yang1 , Sijie Wang1 , Liang Liang1 , Jie Long1 , Changmei Lin1,4 , Yuchan You1,4, Jian Li2 , Qinwei Chen3,7,8 , Kefeng Wu4*, Ruiqing Zhou5*, Shunqing Wang5 , Yongjian Su6 , Zunnan Huang6 , Qing Li7 , Guo Fu7,2,Qiyuan Li 8,3,7*

Aplastic Anemia (AA) is a hematopoietic failure symptom of the bone marrow that can be caused by a variety of factors such as T-cell mediated immune attack, genetic-related somatic mutations, cytogenetic abnormalities, and defective telomerase functions. Recently, Single-cell RNA-sequencing (scRNA-seq) analysis of bone marrow-derived Hematopoietic Stem and Progenitor Cells (HSPCs) from AA patients also revealed the involvement of selective lineage disruption, altered alternative splicing, and polyadenylation in AA pathogenesis . However, these new mechanisms did not provide any new therapeutic approaches for AA, as novel therapies are urgently needed for patients who received no durable benefit from immunosuppressive therapy combined with the Thrombopoietin Receptor (TpoR) activator and patients who underwent allogeneic hematopoietic stem cell transplantation. Therefore, further research is warranted for a deeper understanding of AA and better treatment of this disease.