title: Molecular cytogenetic and clinical findings in ETV6/ABL1-positive leukemia.
abstract: Rearrangements of 12p, resulting from deletions or translocations, are common findings in hematologic malignancies. In many cases, these rearrangements target the ETV6 gene (previously called TEL) located at 12p13. Various partner genes have been implicated in the formation of fusion genes with ETV6. These include PDGFRB, JAK2, NTRK3, ABL2, and ABL1, each of which encodes for proteins with tyrosine kinase activity. To date, ETV6/ABL1 transcripts have been detected in only four patients with a leukemic disorder. Here, we describe one adult with chronic myeloid leukemia and a child with T-cell acute lymphocytic leukemia with ETV6/ABL1. Molecular cytogenetic analysis confirmed that formation of an ETV6/ABL1 fusion in these patients required at least three chromosomal breaks and showed that each of these translocations is the result of a complex chromosomal rearrangement. Molecular analysis showed the presence of two fusion transcripts in both patients as the result of alternative splicing, questioning the suggested role of these transcripts in the lineage specificity. Clinical findings of these patients were compared to those of previously reported cases, and the possible clinical and biological similarities between ETV6/ABL1 and other fusion genes leading to increased tyrosine kinase activity are discussed.
authors.affiliation: Centre for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: H
authors.initials: H
authors.lastname: Van Limbergen
authors.forename: H B
authors.initials: HB
authors.lastname: Beverloo
authors.forename: E
authors.initials: E
authors.lastname: van Drunen
authors.forename: A
authors.initials: A
authors.lastname: Janssens
authors.forename: K
authors.initials: K
authors.lastname: Hählen
authors.forename: B
authors.initials: B
authors.lastname: Poppe
authors.forename: N
authors.initials: N
authors.lastname: Van Roy
authors.forename: P
authors.initials: P
authors.lastname: Marynen
authors.forename: A
authors.initials: A
authors.lastname: De Paepe
authors.forename: R
authors.initials: R
authors.lastname: Slater
authors.forename: F
authors.initials: F
authors.lastname: Speleman
mesh_terms: D002675:Child, Preschool; D002872:Chromosome Deletion; D004268:DNA-Binding Proteins / Q000235:genetics*; D016313:Genes, abl / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000235:genetics*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D004268:DNA-Binding Proteins; D015514:Oncogene Proteins, Fusion; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D014157:Transcription Factors; D000097764:ETS Translocation Variant 6 Protein