Volumen: 18 # Number : 2
Publication Date : Mayo - Agosto Year: 2014
Polymorphisms in GSTP1, GSTM1 and GSTT1 genes are associated
with the risk of relapse in patients
with childhood Acute Lymphobastic Leukemia
Authors: Cotignola J, Leonardi DB, Nuñez M, De Siervi A,
Alfonso G, Riccheri MC, Vazquez E.
Abstract: The prediction of disease progression is one of the biggest challenges in oncology. The aim of this study was to find polymorphisms that help to identify
patients diagnosed with Acute Leukemia (AL) who are at high risk of relapse. We recruited 194 patients with AL from Hospital Posadas. The protocol
was approved by the Ethic Committee and all patients, or guardians, signed an informed consent. Germline DNA was isolated from peripheral blood lymphocytes and 5 polymorphisms were genotyped:
Glutathion-S-Transferases (GSTP1 c.313A>G (p.Ile105Val); GSTM1 null; GSTT1 null), Multiple Drug Resistance gene 1 (ABCB1/MDR1 c.3435T>C), and Methylenetetrahydrofolate Reductase (MTHFR c.665C>T). Two polymorphisms (GSTM1 y GSTT1) were analyzed by multiplex PCR and the other three by PCR-RFLP. We found that the GSTs combined genotype is significantly associated with relapse (p=0.003). When we analyzed only the pediatric patients (n=158) using a multivariate model, we found that the GSTP1 c.313GG genotype increases the risk of relapse (HR=5.4; 95%CI=1.7-17.2; p=0.005). We further restricted the analysis to pediatric patients with Acute Lymphoblastic Leukemia with complete
remission (n=136) and found a similar result (HR=5.6; 95%CI=1.8-17.9; p=0.004). These results show that the genotype of the GSTs might modify the AL progression. The validation of these findings will help to choose a better treatment and follow-up schema for each patient diagnosed with AL according
to their genotype.
Key words: Acute Leukemia, Risk, Relapse,
Genotype, Polymorphism
Pages : 111-116
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