Abstract Summary
Introduction: Acquired pure red cell aplasia (PRCA) is a kind of rare bone marrow failure disease characterized by destruction of erythrocyte by the immune system. Patients with PRCA have a response to immunosuppressive therapy, but myelodysplastic syndromes and acute myeloid leukemia develop in some patients termed clonal evolution. Methods: We performed the targeted sequencing of 32 myeloid neoplasm related genes in 25 patients with primary PRCA. We also conducted the same genetic testing on 32 patients with large granular lymphocytic leukemia (LGLL) associated PRCA for comparison. Results: Myeloid gene mutations were only detected in 39.7% of acquired PRCA who older than 40 years. Gene mutations in primary PRCA patients were mainly enriched in DNA methylation (20.0%) and histone acetylation modification (20.0%), while those in LGLL associated PRCA patients were mainly enriched in DNA methylation (18.8%) and splicing factor (6.3%). The most frequent mutation is DNMT3A with 12.0% in PRCA, 12.5% in LGLL PRCA. Mutations in RUNX1, ASXL1, BCOR, CBL, CEBPA, EZH2, IDH1 and SETBP1 were only found in patients with primary PRCA, and mutations in U2AF1 and MPL were only found in patients with LGLL associated PRCA. Of note, except for IDH2 mutation, the mutation sites of the other genes were completely discordant in the PRCA and LGLL PRCA groups. The Hb levels were significantly higher in primary PRCA patients without mutation. There is no correlation between gene mutations and CsA treatment response. Conclusions: Patients with primary PRCA and LGLL-associated PRCA might have distinct gene mutations.
