title: Chromosome band 16q22-linked familial AML: exclusion of candidate genes, and possible disease risk modification by NQO1 polymorphisms.
abstract: Analyses of chromosomal translocation and inversion breakpoints in sporadic acute myeloid leukemias have identified many transcription factors as playing a role in leukemogenesis. Studies of families with a Mendelian predisposition to hematological malignancies have identified the gene coding for the transcription factor RUNX1 as a leukemia-predisposing gene involved in the first steps of leukemogenesis. Using two families, another autosomal dominant familial leukemia locus was linked to chromosome band 16q22 where the CBFB gene maps. Although CBFB forms a core-binding factor transcriptional complex with RUNX1, previous analyses have excluded the CBFB gene as the leukemia-predisposing gene in these families. In the current study, we performed an extended molecular analysis in these families of the four other transcription factor genes in the 16q22 critical region as well as of two other genes with a known association with leukemia. Several previously undescribed but nonpathogenic sequence variants were identified. We demonstrated that the transcription factors E2F4, CTCF, NFATC3, and NFAT5, and the genes coding for NAD(P)H:quinone oxido-reductase 1 (NQO1) and for E-cadherin are not responsible for the leukemia susceptibility in these families. The presence of NQO1 polymorphisms may suggest a role for this gene in disease risk modification in these families.
authors.affiliation: Genetics and Bioinformatics Division, the Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
authors.forename: Robert
authors.initials: R
authors.lastname: Escher
authors.forename: Antonia
authors.initials: A
authors.lastname: Jones
authors.forename: Fitsum
authors.initials: F
authors.lastname: Hagos
authors.forename: Catherine
authors.initials: C
authors.lastname: Carmichael
authors.forename: Marshall
authors.initials: M
authors.lastname: Horwitz
authors.forename: Olufunmilayo I
authors.initials: OI
authors.lastname: Olopade
authors.forename: Hamish S
authors.initials: HS
authors.lastname: Scott
mesh_terms: D000076246:CCCTC-Binding Factor; D002871:Chromosome Banding / Q000379:methods*; D002875:Chromosomes / Q000648:ultrastructure; D002885:Chromosomes, Human, Pair 16; D004268:DNA-Binding Proteins / Q000378:metabolism; D005799:Genes, Dominant; D008040:Genetic Linkage; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics* / Q000378:metabolism; D050778:NFATC Transcription Factors; D011110:Polymorphism, Genetic; D012097:Repressor Proteins / Q000378:metabolism; D012306:Risk; D012307:Risk Factors; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D004268:DNA-Binding Proteins; C118125:NFAT5 protein, human; D050778:NFATC Transcription Factors; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C445503:transcription factor NF-AT c3; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human