TP53 codon 72 polymorphism predicts chronic myeloid leukemia susceptibility and treatment outcome.
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.213 G>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.213 G>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 50years (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 a;TP53 c.213 G>C may be a potential biomarker of CML susceptibility and clinical outcome.
Laboratorio de Genética Hematológica, IMEX, CONICET-Academia Nacional de Medicina, Buenos Aires, Argentina.
Natalia
N
Weich
Laboratorio de Genética Hematológica, IMEX, CONICET-Academia Nacional de Medicina, Buenos Aires, Argentina.
Cristian
C
Ferri
Servicio de Hematología, Hospital Ramos Mejía, Buenos Aires, Argentina.
Beatriz
B
Moiraghi
Departamento de Hemato-oncología, Academia Nacional de Medicina, Buenos Aires, Argentina.
Raquel
R
Bengió
FUNDALEU, Buenos Aires, Argentina.
Isabel
I
Giere
FUNDALEU, Buenos Aires, Argentina.
Carolina
C
Pavlovsky
Laboratorio de Genética Hematológica, IMEX, CONICET-Academia Nacional de Medicina, Buenos Aires, Argentina.
Irene
I
Larripa
Laboratorio de Genética Hematológica, IMEX, CONICET-Academia Nacional de Medicina, Buenos Aires, Argentina. Electronic address: affundia@hematologia.anm.edu.ar.
Ariela
A
Fundia
D014408:Biomarkers, Tumor / Q000032:analysis; D016022:Case-Control Studies; D003062:Codon / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D017211:Treatment Failure; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D014408:Biomarkers, Tumor; D003062:Codon; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000068877:Imatinib Mesylate
CML biomarker; Chronic myeloid leukemia; TKI treatment response; TP53 polymorphism