title: A novel chromosomal translocation t(3;7)(q26;q21) in myeloid leukemia resulting in overexpression of EVI1.
abstract: The EVI1 proto-oncogene encodes a nuclear zinc finger protein that acts as a transcription repressor factor. In myeloid leukemia it is often activated by chromosomal rearrangements involving band 3q26, where the gene has been mapped. Here we report two leukemia cases [a chronic myeloid leukemia blast crisis (CML-BC) and an acute myeloid leukemia (AML) M4] showing a t(3;7)(q26;q21) translocation in a balanced and unbalanced form, respectively. Fluorescent in situ hybridization (FISH) analysis revealed that both patients showed a breakpoint on chromosome 3 inside the clone RP11-33A1 containing the EVI1 oncogene and, on chromosome 7, inside the clone RP11-322M5, partially containing the CDK6 oncogene which is a D cyclin-dependent kinase gene, observed to be overexpressed and disrupted in many hematological malignancies. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis showed overexpression of EVI1 in both cases, but excluded the presence of any CDK6/ EVI1 fusion transcript. CDK6 expression was also detected. Together, these data indicate that EVI1 activation is likely due not to the generation of a novel fusion gene with CDK6 but to a position effect dysregulating its transcriptional pattern.
authors.affiliation: DAPEG, Section of Genetics, University of Bari, Via Amendola 165/A, 70126 Bari, Italy. c.storlazzi@biologia.uniba.it
authors.forename: C T
authors.initials: CT
authors.lastname: Storlazzi
authors.forename: L
authors.initials: L
authors.lastname: Anelli
authors.forename: F
authors.initials: F
authors.lastname: Albano
authors.forename: A
authors.initials: A
authors.lastname: Zagaria
authors.forename: M
authors.initials: M
authors.lastname: Ventura
authors.forename: M
authors.initials: M
authors.lastname: Rocchi
authors.forename: I
authors.initials: I
authors.lastname: Panagopoulos
authors.forename: A
authors.initials: A
authors.lastname: Pannunzio
authors.forename: E
authors.initials: E
authors.lastname: Ottaviani
authors.forename: V
authors.initials: V
authors.lastname: Liso
authors.forename: G
authors.initials: G
authors.lastname: Specchia
mesh_terms: D000208:Acute Disease; D017398:Alternative Splicing / Q000235:genetics; D001752:Blast Crisis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002874:Chromosome Mapping; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000074008:MDS1 and EVI1 Complex Locus Protein; D008297:Male; D008875:Middle Aged; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D014178:Translocation, Genetic
chemical_list: D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors