IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
MDM2 GENE POLYMORPHISMS IN CHRONIC MYELOID LEUKEMIA: A CASE-CONTROL STUDY IN ARGENTINE
Autor/es:
BENGIO R; WEICH N; MARTINEZ LAHITOU IM; LARRIPA I; FONTECHA MB; MOIRAGHI B; FUNDIA A
Lugar:
Foz de Iguazu
Reunión:
Congreso; INTERNATIONAL CONGRESS OF GENETICS; 2018
Institución organizadora:
Sociedad Argentina de Genética
Resumen:
BCR-ABL1 oncogene is a key molecular marker of chronic myeloid leukemia (CML), but molecular mechanisms that influence disease risk or lead to variable responses to tyrosine kinase inhibitors (TKIs), remain unknown. We have recently shown that that the single nucleotide polymorphism (SNP) TP53 213G>C is associated with CML susceptibility and worse treatment response. Considering that TP53 activity is mainly regulated by MDM2 oncogene, the aim of this study was to perform a case-control study to assess the role of 5 MDM2 polymorphisms in CML. Genomic DNA of 135 treated patients and 136 healthy individuals were evaluated. The MDM2 indel1518 polymorphism and 4 MDM2 SNPs (285G>C, 288G>C, 309T>G and 344T>A) were analyzed by PCR methods and direct sequencing. Treatment failure was detected in 64 patients, 20 of them exhibited BCR-ABL1 mutations. Individual analysis of MDM2 polymorphisms showed no association with CML risk and clinical outcomes. However, patients carrying combined MDM2 in/in-309G/G genotypes exhibited an increased risk of Major Cytogenetic Response failure (p=0.030; OR=7.22; CI:1.17-36.90). The combined analysis of MDM2 polymorphisms with TP53 213G>C genotypes showed that MDM2 in/in-TP53C/C (p=0.015); MDM2 in/del-TP53G/G (p=0.044); MDM2 del/del-TP53G/G (p=0.036) and MDM2 del/del-309T/T-TP53G/G (p=0.030) were associated with low risk to CML. Patients with 3 different variant genotypes for MDM2-indel1518/MDM2-309T>G/TP53-213G>C were associated with low Sokal score (p=0.045; OR=0.19; CI:0.04-0.75). This is the first study that determines the genotype frequencies of these MDM2 polymorphisms in Argentinian patients and controls. Concluding, the combination of MDM2 and TP53 polymorphisms may be related to the risk of CML and treatment outcome.