Pb2034: targeted sequencing landscape of a chinese pure red cell anemia cohort

Topic: 11. Bone marrow failure syndromes incl. PNH - Biology & Translational Research Background: Primary pure red cell aplasia(PRCA) and secondary PRCA associated with large granular lymphocyte leukemia are generally considered to be immune-mediated. The PRCA 2004/2006 study showed that poor responses to immunosuppression and anemia relapse were associated with death. PRCA may represent the prodrome to MDS. However, the underlying mechanism was still unclear. Aims: We investigated gene mutations in myeloid neoplasm-associated genes in PRCA, in order to clarify the gene mutation landscape of PRCA, especially the difference between primary PRCA and T-LGLL associated PRCA. Methods: Clinical characteristics were collected. Extracted genomic DNA samples from peripheral blood were subjected to targeted sequencing for 63 myeloid malignancy-associated genes using a MiSeq system and a TruSight Myeloid Sequencing Panel kit according to Illumina. Heatmaps were generated via Graphpad 9.5. Results: A total of 70 PRCA patients were enrolled in our study, 20 were T-LGLL associated PRCA, 50 were primary PRCA. 37 was males and 43 was females. Median age was 60(22-89) years old. We identified 19 mutations affecting amino acid sequences in of 70 PRCA patients. Overall genomic alterations was shown in Figure 1. Most frequent mutations included TET2(40/70, 57.14%), ASXL1(23/70, 32.86%), GATA2(13/70, 18.57%), MLL(7/70, 10.00%), SETBP1(5/70, 7.14%), RUNX1(4/70, 5.71%), SH2B3(3/70, 4.29%), DNMT3A(3/70, 4.29%). Subgroup analysis of gene mutation frequencies were shown in Figure 2, there was significant difference between T-LGLL associated PRCA and primary PRCA(p<0.05). In primary PRCA group, most frequent mutations included TET2(31/50, 62%), ASXL1(17/50, 34%), GATA2(10/50, 20%), MLL(6/50, 12%), and SETBP1(5/50, 10%). In T-LGLL associated PRCA group, most frequent mutations included TET2(9/20, 45%), ASXL1(6/20, 30%), GATA2(3/20, 15%), DNMT3A(2/20, 10%), and STAT3(2/20, 10%). Summary/Conclusion: We found that rare variants or mutations in myeloid neoplasm-associated genes were detected in PRCA. In our cohort, TET2, ASXL1, GATA2 were frequent in both primary and T-LGLL associated PRCA.Keywords: Somatic mutation, Pure red cell aplasia, T cell leukemia