TP53 codon 72 polymorphism predicts chronic myeloid leukemia susceptibility and treatment outcome

WEICH, N; BENGIÓ, R; LARRIPA, I; ELENA B. MOIRAGHI; PAVLOVSKY, C; FERRI, C; GIERE, I; FUNDIA, A

BLOOD CELLS MOLECULES AND DISEASES

ACADEMIC PRESS INC ELSEVIER SCIENCE

Lugar: Amsterdam; Año: 2016 vol. 59 p. 129 - 133

1079-9796

BCR-ABL1 gene is a key molecular marker of chronic myeloid leukemia (CML), but it is still unclear which molecular factors may influence CML risk or lead to variable responses to tyrosine kinase inhibitors (TKIs). The aim of this study was to investigate the impact of TP53 c.213G>C (Arg72Pro; rs1042522) polymorphism on CML risk and its correlation with clinical outcome. Peripheral blood samples from 141 treated CML patients and 141 sex- and age-matched healthy individuals were genotyped by PCR-RFLP. Standard genetic models for disease penetrance were evaluated by logistic regression analysis and Kaplan-Meier method was performed to estimate survival curves. Our study suggests that TP53 c.213G>C polymorphism may be involved in CML development considering a recessive model (p=0.01; OR: 0.19; CI: 0.06-0.68). In addition, a non-homogenous distribution was found for this polymorphism in males and patients youngers than 50 years (p=0.02). According to clinical response, TP53-GG genotype was associated with higher levels of BCR-ABL1 transcripts (p=0.04) and shorter event free survival (p=0.04). Moreover, a trend toward significance was found for failure free survival (p=0.06) and time to imatinib failure (p=0.08). In conclusion, our data suggest that TP53 c.213G>C may be a potential biomarker of CML susceptibility and clinical outcome.