Mutations of ASXL1 and TET2 in aplastic anemia.

Acquired aplastic anemia (AA), characterized by pancytopenia in peripheral blood (PB) and bone marrow (BM) hypoplasia, is a bone marrow failure syndrome. The late evolution to myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML) is the most common clonal complication in refractory patients and in those who do not achieve a robust response. The reported rates of clonal evolution varied in some studies from 1.7%-57% during an observation period of 5-11 years. The evolution of chromosomal abnormalities including monosomy 7 has been associated with a poor prognosis, but some abnormal cytogenetics, for example, +8 and del13q, have been associated with a good response to immunosuppressive therapy (IST). Single nucleotide polymorphism array karyotype abnormalities could identify those AA patients who were at risk of clonal evolution. Mutations of DNMT3A and BCOR may be associated with a risk of transformation to MDS. However, no reliable biomarkers that predict prognosis and MDS evolution are currently known in AA. AA has genetic instability, and acquired somatic mutations of ASXL1, TET2, RUNX1, TP53, K-RAS and N-RAS typically occurred in MDS/AML. We postulated that these mutations might be an early event in AA evolution to MDS/AML, and could predict MDS/AML evolution and prognosis. In this study, we analyzed mutations in ASXL1, TET2, RUNX1, TP53, K-RAS and N-RAS in Chinese AA patients and showed that somatic mutations that were common in myeloid malignancies also existed in AA. Moreover, patients with different mutations showed distinct clinical and biological features. Bone marrow aspirates were collected from 440 patients with pancytopenia between February 2012 and September 2014 at a single institution (Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College). A total of 138 patients with AA diagnosed according to standard criteria had complete clinical data for this study; 16 iron deficiency anemia or megaloblastic anemia patients (age range 32-77 years) were analyzed as controls. Tables 1 and 2 list the clinical and biological characteristics of these AA patients.