Clonal hematopoiesis (CH) in AA. (A) A schematic diagram depicting the relationship between the autoimmune pathogenesis of AA and the emergence of CH. The autoimmune attack (lightning symbol) on HSPCs (gray circles) by cytotoxic T lymphocytes leads to bone marrow (BM) aplasia. After the patients achieve hematopoietic recovery following immunosuppressive therapy (IST), they may develop the clonal expansion of cells bearing somatic mutations (circles of different colors) due to a relative growth or survival advantage conferred by somatic mutations. (B) A schematic diagram illustrating various treatment outcomes that may affect clonal evolution, including achievement of complete remission (CR), partial remission (PR), or having refractory disease following IST. Approximately one-third of the patients will experience a relapse. Some of the patients with relapsed and refractory disease may be salvaged by a second round of IST. (C) With long-term follow-up, 15% to 20% of patients will acquire additional genetic alterations (dark orange circles) and will progress to secondary myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), whereas 20% to 25% of patients will develop hemolytic paroxysmal nocturnal hemoglobinuria (PNH) over the course of their disease (caused by PIGA mutation).