INVESTIGADORES
VAZQUEZ Elba Susana
congresos y reuniones científicas
Título:
THE GLUTATHION-S-TRANFERASE PI (GSTP1) 105 ILE>VAL POLYMORPHISM MIGHT BE ASSOCIATED WITH POORER RECURRENCE-FREE SURVIVAL IN PEDIATRIC PATIENTS DIAGNOSED WITH ACUTE LEUKEMIA
Autor/es:
COTIGNOLA JAVIER; RICCHERI MARIA CECILIA; DE SIERVI ADRIANA; ALFONSO GRACIELA; MATUS MONICA; VAZQUEZ ELBA
Lugar:
Boston, USA
Reunión:
Congreso; SIOP, International Society of Pediatric Cancer; 2010
Institución organizadora:
SIOP, International Society of Pediatric Cancer
Resumen:
One of the most challenging issues in oncology is the prediction of disease progression and response to therapy. The inter-individual differences in response to drugs are due, at least in part, to genetic polymorphisms. Therefore, the aim of this project is to identify genetic markers that might help to predict acute leukemia (AL) progression, resistance to chemotherapy and/or development of therapy-related side effects. We have recruited pediatric patients diagnosed with AL from one Hospital Center in Buenos Aires. The protocol was approved by the Ethic Committee and follows the ethical principles for medical research involving human subjects enunciated by the Declaration of Helsinki. Patients’ relatives or guardians signed an informed consent before sample donation. We draw peripheral blood and extracted lymphocyte DNA. We genotyped 6 polymorphisms (4 SNPs and 2 gene deletions) within genes related to xenobiotic metabolism: glutathione-s-transferases (GSTP1 105 I>V, rs1695; GSTT1 null; GSTM1 null), ATP-binding cassette B1/multidrug resistance gene 1 (ABCB1/MDR1 3435 C>T, rs1045642), cytidine deaminase (CDA -451 C>T, rs532545), and 5,10-methylenetetrahydrofolate reductase (MTHFR 677 C>T, rs1801133). GSTT1 and GSTM1 polymorphisms were assessed by PCR multiplex reactions, and the rest by PCR-RFLP. Preliminary results from 100 specimens showed a non-significant trend to a higher frequency of GSTM1 null genotype in pediatric AL (60%) compared to adult AL (25%) (Fisher p=0.07). We also found that homozygote patients for the GSTP1 105 V allele had poorer recurrence-free survival compared to homozygote GSTP1 105 I patients (log-rank p=0.03). Our findings show that GSTP1 and GSTM1 polymorphisms might be involved in AL development and progression. The study of GST polymorphisms might become an important tool to choose the best follow-up schema for each patient; increasing the survival and quality of life. Therefore, these results warrant the study of more AL patients and performing multivariate analyzes.