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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 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 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.

Registro:

Documento: Artículo
Título:Improving risk stratification of patients with childhood acute lymphoblastic leukemia: Glutathione-S-Transferases polymorphisms are associated with increased risk of relapse
Autor:Leonardi, D.B.; Abbate, M.; Riccheri, M.C.; Nuñez, M.; Alfonso, G.; Gueron, G.; De Siervi, A.; Vazquez, E.; Cotignola, J.
Filiación: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
Departamento de Hematología Pediátrica, Hospital Nacional Profesor A. Posadas, Pte. Illia s/n (1684), El Palomar, Buenos Aires, Argentina
Departamento de Matemáticas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954 (1113), Caba, Argentina
Departamento de Hematología, Hospital Nacional Profesor A. Posadas, Pte. Illia s/n (1684), El Palomar, Buenos Aires, Argentina
Laboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Vuelta de Obligado 2490 (1428), Caba, Argentina
Palabras clave:Acute leukemia; Glutathione-S-Transferase; Polymorphism; Predictor; Relapse; glutathione transferase; glutathione transferase M1; glutathione transferase P1; glutathione transferase T1; multidrug resistance protein 1; acute lymphoblastic leukemia; adolescent; adult; Article; cancer prognosis; cancer risk; cancer survival; child; childhood leukemia; controlled study; female; gene; gene frequency; genetic association; genetic risk; genetic variability; genotype; GSTM1 gene; GSTP1 gene; GSTT1 gene; high risk population; human; infant; leukemia relapse; major clinical study; male; MDR1 gene; MTHFR gene; multiplex polymerase chain reaction; newborn; predictive value; recurrence free survival; retrospective study; risk assessment; single nucleotide polymorphism; survival analysis
Año:2017
Volumen:8
Número:1
Página de inicio:110
Página de fin:117
DOI: http://dx.doi.org/10.18632/oncotarget.8606
Título revista:Oncotarget
Título revista abreviado:Oncotarget
ISSN:19492553
CAS:glutathione transferase, 50812-37-8
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19492553_v8_n1_p110_Leonardi

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Citas:

---------- APA ----------
Leonardi, D.B., Abbate, M., Riccheri, M.C., Nuñez, M., Alfonso, G., Gueron, G., De Siervi, A.,..., Cotignola, J. (2017) . Improving risk stratification of patients with childhood acute lymphoblastic leukemia: Glutathione-S-Transferases polymorphisms are associated with increased risk of relapse. Oncotarget, 8(1), 110-117.
http://dx.doi.org/10.18632/oncotarget.8606
---------- CHICAGO ----------
Leonardi, D.B., Abbate, M., Riccheri, M.C., Nuñez, M., Alfonso, G., Gueron, G., et al. "Improving risk stratification of patients with childhood acute lymphoblastic leukemia: Glutathione-S-Transferases polymorphisms are associated with increased risk of relapse" . Oncotarget 8, no. 1 (2017) : 110-117.
http://dx.doi.org/10.18632/oncotarget.8606
---------- MLA ----------
Leonardi, D.B., Abbate, M., Riccheri, M.C., Nuñez, M., Alfonso, G., Gueron, G., et al. "Improving risk stratification of patients with childhood acute lymphoblastic leukemia: Glutathione-S-Transferases polymorphisms are associated with increased risk of relapse" . Oncotarget, vol. 8, no. 1, 2017, pp. 110-117.
http://dx.doi.org/10.18632/oncotarget.8606
---------- VANCOUVER ----------
Leonardi, D.B., Abbate, M., Riccheri, M.C., Nuñez, M., Alfonso, G., Gueron, G., et al. Improving risk stratification of patients with childhood acute lymphoblastic leukemia: Glutathione-S-Transferases polymorphisms are associated with increased risk of relapse. Oncotarget. 2017;8(1):110-117.
http://dx.doi.org/10.18632/oncotarget.8606