Gene Mutation Profiles of Primary Pure Red Cell Aplasia and Large Granular Lymphocytic Leukemia Associated Pure Red Cell Aplasia

Acquired pure red cell aplasia (PRCA) is a kind of rare bone marrow failure disease characterized by destruction of erythrocyte by the immune system. However, the gene mutation profile of acquired PRCA remains obscure. Herein, we performed the targeted sequencing of 32 disease-related genes in 25 patients with primary PRCA and 32 patients with large granular lymphocytic leukemia (LGLL)-associated PRCA to reveal the mutational landscape of acquired PRCA, who were registered in Chinese Eastern Collaboration Group of Anemia (CECGA). Also, the T cell receptor (TCR) sequencing data of 8 patients with primary PRCA and 25 patients with LGLL-associated PRCA were collected to reveal the T cell clonotypes. The gene mutation was detected in 39.7% of acquired PRCA with a limited number of myeloid cancer candidate genes. 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 the IDH2 mutation, the mutation sites of other genes were completely discordant in the PRCA and LGLL-PRCA groups. For LGLL-associated PRCA patients, TRBV6_TRBJ2, as a main clonotype was counted as a higher number during the disease period, as well as the number of clonotypes were relatively lower than that of the primary PRCA patients. The Hb levels were significantly higher in primary PRCA patients without mutation (P=0.0165). The ferritin level in patients with mutation was significantly higher (P=0.0217), in patients with LGLL-associated PRCA. This study describes and compares the mutation characteristics of primary PRCA and LGLL-associated PRCA.

He:LongBioPharmaceuticals: Consultancy, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy, Other: All authors received support for third-party writing assistance, furnished by Scott Battle, PhD, CMPP, of Nucleus Global, an Inizio company, and funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland..