A polymorphism in the TYMP gene is associated with the outcome of HLA‐identical sibling allogeneic stem cell transplantation

Abstract

Thymidine phosphorylase (TYMP), an enzyme involved in nucleotide synthesis, has been implicated in critical biological processes such as DNA replication, protection against mutations, and tissue repair. In this work, we retrospectively evaluated the influence of a polymorphism in the TYMP gene (rs112723255; G/A) upon the outcome of 448 patients subjected to allogeneic stem cell transplantation (allo‐SCT) from an human leukocyte antigen (HLA)‐identical sibling donor. The TYMP genotype of patients correlated with overall survival—carriers of the minor allele (A) being at an increased risk of dying after transplantation (hazard ratio, HR = 1.9; P = 0.004). This effect was mostly due to differences in transplant toxicity‐related mortality (HR = 2.5; P = 0.029). In addition, the TYMP genotype of donors was associated with the risk of chronic graft‐versus‐host disease (GVHD)—carriers of the minor allele being at an increased risk of developing this complication ([HR] = 1.7; P = 0.039). The impact of such polymorphism on the risk of chronic GVHD is limited to patients transplanted in early stage disease (HR = 2.2; P = 0.019). The combination of a donor harboring the minor allele with a patient homozygous for the major allele was associated with the highest risk of chronic GVHD (HR = 2.8; P = 0.008). These findings provide the first evidence of the significant impact of the TYMP genotype upon the clinical outcome of patients treated with HLA‐identical sibling allo‐SCT. Am. J. Hematol. 88:883–889, 2013. © 2013 Wiley Periodicals, Inc.

Thymidine phosphorylase: A potential new target for treating cardiovascular disease

“…Targeting TYMP may be considered a potential immunotherapy for cancer. Guillem and colleagues recently provided the first epidemiological evidence of the TYMP gene SNP (rs112723255) effectively acting as a minor histocompatibility antigen [114]. This finding is in agreement with a previous study and suggests that TYMP is a potential target for cancer immunotherapy [115].…”

Construction of a Lactate-Related Prognostic Signature for Predicting Prognosis, Tumor Microenvironment, and Immune Response in Kidney Renal Clear Cell Carcinoma

“…In patients with KIRC, a decreased expression of HADH was also related to immune infiltration and poor prognosis ( 58 ). TYMP, also known as a platelet-derived endothelial cell growth factor, catalyzes the reversible phosphorolysis of thymidine ( 59 ). TYMP was shown to be upregulated in multiple solid tumors, where it is implicated in cell proliferation and angiogenesis ( 60 ).…”

“…Our results suggested that the expression of TYMP was notably related to the expression of several immunocyte markers and might be involved in regulating the immune response. Many studies have indicated that TYMP was a potential target for cancer immunotherapy ( 59 , 61 ). Our study suggested that the prognostic value of these three LRGs in KIRC and the mechanism of the three genes in KIRC need further investigation.…”

Renal Cell Carcinoma as a Metabolic Disease: An Update on Main Pathways, Potential Biomarkers, and Therapeutic Targets

“…Thymidine phosphorylase (TYMP), a platelet-derived endothelial cell growth factor, is overexpressed in tumor cells and surrounding extra matrix cells. It catalyzes the reversible phosphorolysis of thymidine [64] and is upregulated in multiple solid tumors [65]. This protein was associated with the expression of a number of immunocyte markers and may have a function in controlling the immunological response, indicating its potential relevance as an immunotherapy target [64,66].…”