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Improving risk stratification of patients with childhood acute lymphoblastic leukemia: Glutathione-S-Transferases polymorphisms are associated with increased risk of relapse

2016; Impact Journals LLC; Volume: 8; Issue: 1 Linguagem: Inglês

10.18632/oncotarget.8606

1949-2553

Daiana B. Leonardi, Mercedes Abbate, María Cecilia Riccheri, Myriam Núñez, Graciela Alfonso, Geraldine Gueron, Adriana De Siervi, Elba S. Vázquez, Javier Cotignola,

Folate and B Vitamins Research

// Daiana B. Leonardi 1, * , Mercedes Abbate 1, * , María C. Riccheri 2 , Myriam Nuñez 3 , Graciela Alfonso 4 , Geraldine Gueron 1 , Adriana De Siervi 5 , Elba Vazquez 1 , Javier Cotignola 1 1 Laboratorio de Inflamación y Cáncer, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales-Universidad de Buenos Aires, IQUIBICEN-CONICET, Intendente Güiraldes 2160 (1428), CABA, Argentina 2 Departamento de Hematología Pediátrica, Hospital Nacional Profesor A. Posadas, Pte. Illia s/n (1684), El Palomar, Buenos Aires, Argentina 3 Departamento de Matemáticas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954 (1113), CABA, Argentina 4 Departamento de Hematología, Hospital Nacional Profesor A. Posadas, Pte. Illia s/n (1684), El Palomar, Buenos Aires, Argentina 5 Current Affiliation: Laboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos, Instituto de Biología y Medicina Experimental (IBYME–CONICET), Vuelta de Obligado 2490 (1428), CABA, Argentina * These authors contributed equally to this work Correspondence to: Javier Cotignola, email: jcotignola@qb.fcen.uba.ar Keywords: acute leukemia, Glutathione-S-Transferase, polymorphism, predictor, relapse Received: October 23, 2015 Accepted: March 10, 2016 Published: April 06, 2016 ABSTRACT The inclusion of genotype at Acute Lymphoblastic Leukemia (ALL) diagnosis as a genetic predictor of disease outcome is under constant study. However, results are inconclusive and seem to be population specific. We analyzed the predictive value of germline polymorphisms for childhood ALL relapse and survival. We retrospectively recruited 140 Argentine patients with de novo ALL. Genotypes were analyzed using PCR-RFLP ( GSTP1 c.313A > G, MDR1 c.3435T > C, and MTHFR c.665C > T) and multiplex PCR ( GSTT1 null, GSTM1 null). Patients with the GSTP1 c.313GG genotype had an increased risk for relapse in univariate (OR = 2.65, 95% CI = 1.03–6.82, p = 0.04) and multivariate (OR = 3.22, 95% CI = 1.17–8.83, p = 0.02) models. The combined genotype slightly increased risk for relapse in the univariate (OR = 2.82, 95% CI = 1.09–7.32, p = 0.03) and multivariate (OR = 2.98, 95% CI = 1.14–7.79, p = 0.03) models for patients with 2/3-risk-genotypes ( GSTT1 null, GSTM1 null, GSTP1 c.313GG). The Recurrence-Free Survival (RFS) was shorter for GSTP1 c.313GG ( p = 0.025) and 2/3-risk-genotypes ( p = 0.021). GST polymorphisms increased the risk of relapse and RFS of patients with childhood ALL. The inclusion of these genetic markers in ALL treatment protocols might improve risk stratification and reduce the number of relapses and deaths.