Mdr-1 And Gst Polymorphisms Are Involved In Myelodysplasia Progression.

dc.creatorPalodetto, Bruna
dc.creatorde Melo Campos, Paula
dc.creatorBenites, Bruno Deltreggia
dc.creatorde Lourdes Lopes Ferrari Chauffaille, Maria
dc.creatorVelloso, Elvira Deolinda Rodrigues Pereira
dc.creatorTraina, Fabiola
dc.creatorSaad, Sara Teresinha Olalla
dc.date2013-Aug
dc.date2015-11-27T13:31:44Z
dc.date2015-11-27T13:31:44Z
dc.date.accessioned2018-03-29T01:17:48Z
dc.date.available2018-03-29T01:17:48Z
dc.identifierLeukemia Research. v. 37, n. 8, p. 970-3, 2013-Aug.
dc.identifier1873-5835
dc.identifier10.1016/j.leukres.2013.04.024
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/23684483
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/200637
dc.identifier23684483
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1300870
dc.descriptionMyelodysplastic 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.
dc.description37
dc.description970-3
dc.languageeng
dc.relationLeukemia Research
dc.relationLeuk. Res.
dc.rightsfechado
dc.rightsCopyright © 2013 Elsevier Ltd. All rights reserved.
dc.sourcePubMed
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 And Over
dc.subjectAryl Hydrocarbon Hydroxylases
dc.subjectBase Sequence
dc.subjectCytochrome P-450 Cyp2b6
dc.subjectDisease Progression
dc.subjectGenetic Predisposition To Disease
dc.subjectGenotype
dc.subjectGlutathione Transferase
dc.subjectHumans
dc.subjectKaplan-meier Estimate
dc.subjectMiddle Aged
dc.subjectMultiplex Polymerase Chain Reaction
dc.subjectMyelodysplastic Syndromes
dc.subjectNad(p)h Dehydrogenase (quinone)
dc.subjectOutcome Assessment (health Care)
dc.subjectOxidoreductases, N-demethylating
dc.subjectP-glycoprotein
dc.subjectP-glycoproteins
dc.subjectPolymorphism, Genetic
dc.subjectPolymorphism, Restriction Fragment Length
dc.subjectProportional Hazards Models
dc.subjectSequence Deletion
dc.subjectYoung Adult
dc.titleMdr-1 And Gst Polymorphisms Are Involved In Myelodysplasia Progression.
dc.typeArtículos de revistas


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