2019 Volume 60 Issue 5 Pages 417-422
Acquired aplastic anemia (AA) is a hematopoietic disorder caused by an immunologic attack on hematopoietic stem cells (HSCs). The presence of cells with a paroxysmal nocturnal hemoglobinuria (PNH) phenotype or with copy-number neutral loss of heterozygosity of chromosome 6p (6pLOH) suggests an immune-mediated pathophysiology underlying AA. Recently, genomic studies have revealed clonal hematopoiesis by HSCs with altered genes. PIGA, DNMT3A, ASXL1, BCOR, 6pLOH, and HLA class I allele mutations are common in patients with AA. The genomic landscape of AA is distinct from that of the myelodysplastic syndrome or age-related clonal hematopoiesis. This suggests that escape from an autoimmune attack is strongly associated with clonal hematopoiesis in AA. Eltrombopag (EPAG), a thrombopoietin receptor agonist, has recently emerged as a novel therapeutic agent for AA. Further studies are needed to clarify whether EPAG induces clonal expansion of these clones.
