Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Institute of Clinical Pharmacology, Anhui Medical University, Hefei 230032, PR China.
Department of Hematology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, PR China.
Int Immunopharmacol. 2023 Apr;117:110036. doi: 10.1016/j.intimp.2023.110036. Epub 2023 Mar 20.
Acquired aplastic anemia (AA) is an autoimmune disease of bone marrow failure mediated by abnormally activated T cells, manifested by severe depletion of hematopoietic stem and progenitor cells (HSPCs) and peripheral blood cells. Due to the limitation of donors for hematopoietic stem cell transplantation, immunosuppressive therapy (IST) is currently an effective first-line treatment. However, a significant proportion of AA patients remain ineligible for IST, relapse, and develop other hematologic malignancies, such as acute myeloid leukemia after IST. Therefore, it is important to elucidate the pathogenic mechanisms of AA and to identify treatable molecular targets, which is an attractive way to improve these outcomes. In this review, we summarize the immune-related pathogenesis of AA, pharmacological targets, and clinical effects of the current mainstream immunosuppressive agents. It provides new insight into the combination of immunosuppressive drugs with multiple targets, as well as the discovery of new druggable targets based on current intervention pathways.
获得性再生障碍性贫血（AA）是一种由异常激活的 T 细胞介导的骨髓衰竭性自身免疫性疾病，表现为造血干细胞和祖细胞（HSPCs）及外周血细胞严重耗竭。由于造血干细胞移植供体的限制，目前免疫抑制治疗（IST）是一种有效的一线治疗方法。然而，相当一部分 AA 患者仍不符合 IST 条件，复发后会发展为其他血液系统恶性肿瘤，如 IST 后的急性髓系白血病。因此，阐明 AA 的发病机制并确定可治疗的分子靶点非常重要，这是改善这些结果的一种有吸引力的方法。在这篇综述中，我们总结了 AA 的免疫相关发病机制、目前主流免疫抑制剂的药理靶点和临床疗效。它为基于当前干预途径的免疫抑制剂与多靶点联合以及新的可用药靶点的发现提供了新的见解。
