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Type: Artigo de periódico
Title: Mdr-1 And Gst Polymorphisms Are Involved In Myelodysplasia Progression.
Author: Palodetto, Bruna
de Melo Campos, Paula
Benites, Bruno Deltreggia
de Lourdes Lopes Ferrari Chauffaille, Maria
Velloso, Elvira Deolinda Rodrigues Pereira
Traina, Fabiola
Saad, Sara Teresinha Olalla
Abstract: Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders characterized by abnormal hematopoietic differentiation and maturation, which progress toward acute leukemia in approximately 30% of the cases. Drug metabolism polymorphisms in Cytochrome P450 2B6 (CYP2B6), Glutathione S-transferase (GST) and Dehydrogenase Quinone 1 (NQO1) enzymes and P-glycoprotein (MDR-1) could modify enzyme activity. Thus, the aim of this study was to identify the influence of CYP2B6 G15631T, GSTT1, GSTM1, NQO1 C609T and MDR-1 C3435T polymorphisms on MDS progression. We analyzed 78 MDS patients using the PCR-RFLP and multiplex method. The frequency of GST deletions and MDR-1 CC genotype was lower in progression-free patients compared to patients with progression; GST: 17% vs. 35% (P=0.018); MDR-1 gene: 19% vs. 48% (P=0.012). We also verified the influence of GST deletions and MDR-1 C3435T on patient overall survival and found no significant difference (RR=0.75; P=0.599 and RR=0.79; P=0.594 respectively). We concluded that GSTM1 deletion may contribute toward MDS progression probably due to toxic metabolite accumulation which generates cell toxicity and DNA damage. Moreover, MDR-1 C3435T may have a protective effect against MDS progression because the expected lower expression of P-glycoprotein would lead to a higher degree of cell death. To the best of our knowledge, this is the first study showing the relationship of these polymorphisms with MDS progression.
Subject: Adult
Aged, 80 And Over
Aryl Hydrocarbon Hydroxylases
Base Sequence
Cytochrome P-450 Cyp2b6
Disease Progression
Genetic Predisposition To Disease
Glutathione Transferase
Kaplan-meier Estimate
Middle Aged
Multiplex Polymerase Chain Reaction
Myelodysplastic Syndromes
Nad(p)h Dehydrogenase (quinone)
Outcome Assessment (health Care)
Oxidoreductases, N-demethylating
Polymorphism, Genetic
Polymorphism, Restriction Fragment Length
Proportional Hazards Models
Sequence Deletion
Young Adult
Citation: Leukemia Research. v. 37, n. 8, p. 970-3, 2013-Aug.
Rights: fechado
Identifier DOI: 10.1016/j.leukres.2013.04.024
Date Issue: 2013
Appears in Collections:Unicamp - Artigos e Outros Documentos

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