A Sequence Variation in the Promoter Region of PTPN22 Gene Predicts Relapse After HLA-Fully-Matched Unrelated Bone Marrow Transplantation for Hematologic Malignancies

The protein tyrosine phosphatase non-receptor 22 (PTPN22), also known as LYP, is an intracellular phosphatase ubiquitously expressed with particularly high expression in hematopoietic tissues that is a critical negative regulator of signaling through the T cell receptor and has emerged as the strongest common genetic risk factor for human autoimmunity outside the major histocompatibility complex. In this study we analyzed the impact of the polymorphism rs2488457 (1123G>C) in the promoter region of PTPN22 gene on transplant outcomes in patients undergoing unrelated HLA-matched bone marrow transplantation (BMT) through the Japan Donor Marrow Program. The PTPN22 rs2488457 genotypes were retrospectively analyzed in a cohort of 663 patients with hematologic malignancies and their unrelated donors. The presence of the C/C or C/G genotype in the donor side was associated with a significantly lower incidence of relapse compared to the donor G/G genotype (28% vs. 34% 5-years, P =0.05) (Fig.1). No difference was noted in transplant-related mortality, or graft-versus-host disease in relation to the rs2488457 polymorphism. The donor C/C or C/G genotype remained statistically significant for relapse in the multivariate analyses (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.43 to 0.85; P =0.004). These differences in relapse did not significantly affect on overall survival (OS) (48% vs. 49% 5-years, P =0.85). The recipient PTPN22 genotypes did not significantly influence the transplant outcomes. These results suggest an association of the donor C/C or C/G genotype with lower disease relapse. These could therefore be useful in selecting the donor and creating therapeutic strategies for improving the final outcome of allogeneic BMT.