Improving risk stratification of patients with childhood acute lymphoblastic leukemia: Glutathione-S-Transferases polymorphisms are associated with increased risk of relapse
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Daiana B. Leonardi1,*, Mercedes Abbate1,*, María C. Riccheri2, Myriam Nuñez3, Graciela Alfonso4, Geraldine Gueron1, Adriana De Siervi5, Elba Vazquez1, Javier Cotignola1
1Laboratorio 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
2Departamento de Hematología Pediátrica, Hospital Nacional Profesor A. Posadas, Pte. Illia s/n (1684), El Palomar, Buenos Aires, Argentina
3Departamento de Matemáticas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954 (1113), CABA, Argentina
4Departamento de Hematología, Hospital Nacional Profesor A. Posadas, Pte. Illia s/n (1684), El Palomar, Buenos Aires, Argentina
5Current 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
Javier Cotignola, email: [email protected]
Keywords: acute leukemia, Glutathione-S-Transferase, polymorphism, predictor, relapse
Received: October 23, 2015 Accepted: March 10, 2016 Published: April 06, 2016
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.
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