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Infant ALL

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

Leukemia volume 19, pages 214–216 (2005)Cite this article

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.

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Acknowledgements

This work was supported in part by project Ministero Sanità 01, X, 000177; Fondazione Città della Speranza; Progetto finalizzato MIUR-CNR; Compagnia di S Paolo; Fondazione CARIGE.

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Authors and Affiliations

  1. Hematology Unit, Department of Pediatric Hemato-Oncology, G Gaslini Children's Hospital, Genova, Italy

    M Lanciotti, C Dufour, P Di Michele, S Pigullo & C Micalizzi

  2. Centro Ricerca Tettamanti, Pediatric Clinic, University of Milano Bicocca, Monza, Italy

    L Corral & A Biondi

  3. Hematology Division, Bambin Gesù Children's Hospital, Roma, Italy

    G De Rossi & M Luciani

  4. Pediatric Onco-Hematology Clinic University of Padova, Padova, Italy

    G Basso & A Leszl

  5. Center of Pediatric Hemato-Oncology, University of Catania, Catania, Italy

    L Lo Nigro

  6. Section of Medical Statistics, University of Milano-Bicocca, Monza, Italy

    M G Valsecchi

  7. Epidemiology and Biostatistics Section, Scientific Directorate G Gaslini Children's Hospital, Genova, Italy

    R Haupt

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  1. M Lanciotti
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  2. C Dufour
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  3. L Corral
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  9. M Luciani
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  10. L Lo Nigro
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  13. A Biondi
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  14. R Haupt
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Correspondence to M Lanciotti.

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Lanciotti, M., Dufour, C., Corral, L. et al. Genetic polymorphism of NAD(P)H:quinone oxidoreductase is associated with an increased risk of infant acute lymphoblastic leukemia without MLL gene rearrangements. Leukemia 19, 214–216 (2005). https://doi.org/10.1038/sj.leu.2403613

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  • DOI: https://doi.org/10.1038/sj.leu.2403613

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