INVESTIGADORES
DE SIERVI Adriana
artículos
Título:
Improving risk stratification of patients with childhood acute lymphoblastic leukemia: Glutathione-S-Transferases polymorphisms are associated with increased risk of relapse
Autor/es:
LEONARDI D; ABBATE M; RICCHERI C; NUÑEZ M; ALFONSO G; GUERON G; DE SIERVI A; VAZQUEZ ES; COTIGNOLA J
Revista:
Oncotarget
Editorial:
Impact Journals
Referencias:
Año: 2017 vol. 8 p. 110 - 117
Resumen:
The inclusion of genotype at Acute Lymphoblastic Leukemia (ALL) diagnosis asa genetic predictor of disease outcome is under constant study. However, results areinconclusive and seem to be population specific. We analyzed the predictive value ofgermline polymorphisms for childhood ALL relapse and survival. We retrospectivelyrecruited 140 Argentine patients with de novo ALL. Genotypes were analyzed using PCRRFLP(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 increasedrisk 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 slightlyincreased 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 with2/3-risk-genotypes (GSTT1 null, GSTM1 null, GSTP1 c.313GG). The Recurrence-FreeSurvival (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 withchildhood ALL. The inclusion of these genetic markers in ALL treatment protocols mightimprove risk stratification and reduce the number of relapses and deaths.