Study of NAD(P)H: Quinone Oxidoreductase-1 Gene Polymorphism in AML in Correlation to Treatment and Prognosis
Background: NAD(P)H Quinone Oxidoreductase is a flavoenzyme
that plays an important role in protection of cells from oxidative
oxygen damage. The polymorphism in position 609 in exon 6(C® T}
in the human NQO1 gene leads to a proline to serine substitution at
position 187 in the amino acid structure of the NQO1 protein
resulting in loss of enzyme activity.
Aim of the present work was to study the frequency of NQO1 gene
polymorphism in acute myeloid leukemia (AML) patients and its
impact on treatment and prognosis.
Methods: Our study was conducted on 30 newly diagnosed patients
with AML (GP I) and 20 age and sex matched normal healthy
controls. All cases were subjected at diagnosis to thorough history
taking, clinical examination, routine investigations, hematological
assessment including complete blood picture and bone marrow
examination with immunophenotyping , and PCR restriction fragment
length polymorphism of the NQO1 gene. After receiving the first
cycle of induction chemotherapy patients were re-evaluated to assess
their response to treatment.
Results: 80% of our AML patients had a heterozygous mutation of
the NQO1 gene, while the mutation was homozygous in 6.7% of
patients. On the other hand, 10% of our controls had a heterozygous
mutation of the NQO1 gene. The effect of the NQO1 gene
polymorphism on the risk of AML was similar for both males and
females and for smokers and non smokers. There were no significant
differences regarding this polymorphism among different
morphological ( FAB ) subtypes of AML. Remission response to
chemotherapy was lower in patients harboring the mutant type of
NQO1 gene than in patients with the wild type although this finding
was statistically insignificant.
Key words: NQO-1 Polymorphism, AML