Improving risk stratification of patients with childhood acute lymphoblastic leukemia: Glutathione-S-Transferases polymorphisms are associated with increased risk of relapse
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...
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todo:paper_19492553_v8_n1_p110_Leonardi2023-10-03T16:37:17Z Improving risk stratification of patients with childhood acute lymphoblastic leukemia: Glutathione-S-Transferases polymorphisms are associated with increased risk of relapse Leonardi, D.B. Abbate, M. Riccheri, M.C. Nuñez, M. Alfonso, G. Gueron, G. De Siervi, A. Vazquez, E. Cotignola, J. 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 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. Fil:Leonardi, D.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Gueron, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:De Siervi, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Vazquez, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_19492553_v8_n1_p110_Leonardi |
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Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Leonardi, D.B. Abbate, M. Riccheri, M.C. Nuñez, M. Alfonso, G. Gueron, G. De Siervi, A. Vazquez, E. Cotignola, J. Improving risk stratification of patients with childhood acute lymphoblastic leukemia: Glutathione-S-Transferases polymorphisms are associated with increased risk of relapse |
| topic_facet |
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 |
| description |
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. |
| format |
JOUR |
| author |
Leonardi, D.B. Abbate, M. Riccheri, M.C. Nuñez, M. Alfonso, G. Gueron, G. De Siervi, A. Vazquez, E. Cotignola, J. |
| author_facet |
Leonardi, D.B. Abbate, M. Riccheri, M.C. Nuñez, M. Alfonso, G. Gueron, G. De Siervi, A. Vazquez, E. Cotignola, J. |
| author_sort |
Leonardi, D.B. |
| title |
Improving risk stratification of patients with childhood acute lymphoblastic leukemia: Glutathione-S-Transferases polymorphisms are associated with increased risk of relapse |
| title_short |
Improving risk stratification of patients with childhood acute lymphoblastic leukemia: Glutathione-S-Transferases polymorphisms are associated with increased risk of relapse |
| title_full |
Improving risk stratification of patients with childhood acute lymphoblastic leukemia: Glutathione-S-Transferases polymorphisms are associated with increased risk of relapse |
| title_fullStr |
Improving risk stratification of patients with childhood acute lymphoblastic leukemia: Glutathione-S-Transferases polymorphisms are associated with increased risk of relapse |
| title_full_unstemmed |
Improving risk stratification of patients with childhood acute lymphoblastic leukemia: Glutathione-S-Transferases polymorphisms are associated with increased risk of relapse |
| title_sort |
improving risk stratification of patients with childhood acute lymphoblastic leukemia: glutathione-s-transferases polymorphisms are associated with increased risk of relapse |
| url |
http://hdl.handle.net/20.500.12110/paper_19492553_v8_n1_p110_Leonardi |
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| _version_ |
1782024229811650560 |