Immunological links between aplastic anemia and paroxysmal nocturnal hemoglobinuria

Aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH) are closely related bone marrow (BM) failure syndromes linked by shared immunological mechanisms. The frequent emergence of PNH-type blood cells during AA, together with the co-occurrence of the disorders and their overlapping therapeutic responses, supports the concept that they represent a spectrum of immune-mediated hematopoietic injury rather than distinct disease entities.AA is a prototypical immune-mediated BM failure characterized by cytotoxic T-cell-driven suppression of hematopoietic stem and progenitor cells. Within this immune-hostile environment, glycosylphosphatidylinositol (GPI)-anchor-deficient PNH clones commonly emerge and persist, a phenomenon best explained by immune selection rather than intrinsic proliferative advantage. Although most PNH clones detected in AA remain small and clinically silent, their presence reflects ongoing or past immune pressure within the BM microenvironment.Advances in high-sensitivity flow cytometry have revealed that minor PNH populations are frequent in AA, indicating that immune-driven clonal selection occurs at an early stage of hematopoiesis. Longitudinal studies further demonstrate that clonal dynamics parallel changes in immune activity, supporting their relevance for risk-adapted monitoring.In this review, we highlight immune-mediated BM failure as the common soil from which PNH clones arise and discuss implications for diagnosis, monitoring, and phenotype-driven management.