Genetic characterization of acquired aplastic anemia by targeted sequencing

Abstract

Aplastic anemia (AA) is a rare but life-threatening bone marrow failure syndrome; diagnosis is based on cytopenias in peripheral blood and hypocellularity in bone marrow. The distinction between AA and hypocellular myelodysplastic syndrome (MDS) is often difficult to verify, and AA evolves into MDS or AML at a 10-year cumulative incidence of 3.1-9.6%. As AA patients often respond to immunosuppressive therapy, an immune pathophysiology is widely assumed. The evolution of clonal cytogenetic aberrations in hematopoietic cells and the association with clonal paroxysmal nocturnal hemoglobinuria (PNH) suggest that some patients have a clonal hematopoietic disease. Data by Walter and colleagues show that 74% of MDS patients harbor a mutation in at least one of 94 candidate genes, while mutations can still be found in 68% of MDS patients when a core set of 25 genes is analyzed. We hypothesized that mutations that are found in MDS patients may also be present in patients with AA and, therefore, evaluated the mutation profile of 42 genes in AA patients.