[Acquired aplastic anemia: recent advances in pathophysiology and treatment]

Acquired aplastic anemia (AA) is an autoimmune disease caused by T cells specific to hematopoietic stem cells (HSCs). The presence of HLA allele-lacking leukocytes due to uniparental disomy of the short arm of chromosome 6 (6pUPD) or allelic mutations strongly indicates the involvement of such cytotoxic T cells in the pathogenesis of AA. Attempts to improve treatment outcomes by intensification of immunosuppressive therapy (IST) have been unsuccessful. Eltrombopag (EPAG), a thrombopoietin receptor agonist, has recently emerged as a novel therapeutic agent for AA. EPAG directly acts on HSCs and stimulates proliferation, thereby achieving remission in approximately 40% AA patients refractory to IST. However, some cases develop chromosomal aberrations during treatment. Because somatic mutations are common in patients with AA, verifying whether EPAG induces clonal proliferation or evolution of mutant HSCs is critical.