title: Fusion of the homeobox gene HLXB9 and the ETV6 gene in infant acute myeloid leukemias with the t(7;12)(q36;p13).
abstract: Recently, we and others reported a recurrent t(7;12)(q36;p13) found in myeloid malignancies in children < or =18 months of age and associated with a poor prognosis. Fluorescence in situ hybridization studies mapped the 12p13 breakpoint to the first intron of ETV6 and narrowed down the region of 7q36 involved. By using the sequences made public recently by the Human Genome Project, two candidate genes in 7q36 were identified: the homeobox gene HLXB9 and c7orf3, a gene with unknown function. Reverse transcription-PCR of two cases with t(7;12), using primers for c7orf3 and ETV6, was negative. However, reverse transcription-PCR for HLXB9-ETV6 demonstrated alternative splicing; the two major bands corresponded to fusion of exon 1 of HLXB9 to exons 2 and 3, respectively, of ETV6. The reciprocal ETV6-HLXB9 transcript was not detected. It remains to be elucidated if the leukemic phenotype is attributable to the formation of the HLXB9-ETV6 fusion protein, which includes the helix-loop-helix and E26 transformation-specific DNA binding domains of ETV6 or to the disruption of the normal ETV6 protein.
authors.affiliation: Department of Cell Biology and Genetics, Erasmus University Rotterdam, 3000 DR Rotterdam, the Netherlands. beverloo@gen.fgg.eur.nl
authors.forename: H B
authors.initials: HB
authors.lastname: Beverloo
authors.forename: I
authors.initials: I
authors.lastname: Panagopoulos
authors.forename: M
authors.initials: M
authors.lastname: Isaksson
authors.forename: E
authors.initials: E
authors.lastname: van Wering
authors.forename: E
authors.initials: E
authors.lastname: van Drunen
authors.forename: A
authors.initials: A
authors.lastname: de Klein
authors.forename: B
authors.initials: B
authors.lastname: Johansson
authors.forename: R
authors.initials: R
authors.lastname: Slater
mesh_terms: D000208:Acute Disease; D000595:Amino Acid Sequence; D001483:Base Sequence; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007231:Infant, Newborn; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D050783:Proto-Oncogene Proteins c-ets; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D015514:Oncogene Proteins, Fusion; D050783:Proto-Oncogene Proteins c-ets; D012334:RNA, Neoplasm; D012097:Repressor Proteins; D014157:Transcription Factors; D000097764:ETS Translocation Variant 6 Protein; C490003:MNX1 protein, human