[Clonal hematopoiesis in aplastic anemia and paroxysmal nocturnal hemoglobinuria]

Similar with myelodysplastic syndromes (MDS), aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH) are the major bone marrow failure syndromes. Approximately 10-20% of patients with AA/PNH present with transformation into MDS. Clonal hematopoiesis in AA/PNH affected by karyotypic abnormalities and genetic mutations should be discriminated from MDS clone, which is sometimes difficult due to shared genetic events among these diseases. In patients with AA/PNH, clones with UPD6p and PIGA mutations are selected under autoimmune pressure, and those with DNMT3A, ASXL1, and TET2 mutations originated from clonal hematopoiesis of indeterminate potential (CHIP) frequently identified in elderly healthy individuals. In patients with cytopenia, a single CHIP mutation is insufficient for MDS presentation. However, TP53 and U2AF1 mutations, which are not in the list of typical CHIP mutations, are observed in patients with AA with future MDS transformation. Therefore, clonal hematopoiesis in AA/PNH, partially overlapping the MDS clone, is caused by autoimmunity and originates from CHIP, demonstrating distinct genetic profiles.