Genetic polymorphism of NAD(P)H: quinone oxidoreductase is associated with an increased risk of infant acute lymphoblastic leukemia without MLL gene rearrangements

Marina Lanciotti, C. Dufour, L. Corral, P. Di Michele, S. Pigullo, G. De Rossi, G. Basso, A. Leszl, M. Luciani, L. Lo Nigro, C. Micalizzi, M. G. Valsecchi, A. Biondi, R. Haupt

Research output: Contribution to journalArticle

Abstract

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a detoxification enzyme that protects cells against oxidative stress and toxic quinones. A polymorphism (C609T) in the gene produces in the heterozygous individuals (C/T) a reduction and in those homozygous for the variant allele (T/T) the abolishment of NQO1 protein activity. To assess whether NQO1 inactivating polymorphism (CT/TT) was a possible risk factor for infant acute lymphoblastic leukemia (iALL), we investigated the distribution of NQO1 genotype in 50 iALL patients, 32 with MLL gene rearrangements (MLL+) and 18 without (MLL-). As controls, 106 cases of pediatric ALL (pALL), and 147 healthy subjects were also studied. Compared to normal controls, the frequency of the low/null activity NQO1 genotypes was significantly higher in the iALL MLL- (72 vs 38%, P=0.006; odds ratio (OR) 4.22, 95% confidence interval (CI) 1.43-12.49), while no differences were observed in iALL MLL+ (44 vs 38%, P=0.553; OR 1.26, 95% CI 0.58-2.74). Similar results were observed when pALL were used as control. Our results indicate that only the iALL patients without MLL rearrangements had a significantly higher frequency of NQO1 genotypes associated with low/null activity enzyme, suggesting a possible role for NQO1 gene as an MLL-independent risk factor, in the leukemogenic process of this subtype of iALL.

Original languageEnglish
Pages (from-to)214-216
Number of pages3
JournalLeukemia
Volume19
Issue number2
DOIs
Publication statusPublished - Feb 2005

Keywords

  • Infant leukemia
  • MLL gene rearrangement
  • NQO1 polymorphism

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

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