title: The paired box domain gene PAX5 is fused to ETV6/TEL in an acute lymphoblastic leukemia case.
abstract: The PAX5 gene, encoding the B-cell-specific activator protein, is a critical determinant of commitment to the B-lymphocyte pathway. This gene, mapped at 9p13, is juxtaposed to the immunoglobulin heavy chain (IgH) gene as a result of the t(9;14)(p13;q32), a rare but recurring translocation found in a subset of B-cell non-Hodgkin's lymphoma cases. In all of these, this translocation results in deregulated expression of the gene product because of the proximity of IgH. We present here the molecular characterization of a previously reported acute lymphoblastic leukemia case carrying a t(9;12)(q11;p13) translocation. Using 5' rapid amplification of cDNA ends PCR, a novel chimeric transcript was identified that contained the NH(2)-terminal region of PAX5 and most of the ETV6/TEL gene on 12p13. According to the fusion transcript, the resulting chimeric protein would retain the PAX5 paired-box domain and both the helix-loop-helix and DNA binding domains of TEL. Thus, it is reasonable to hypothesize that this protein could act as an aberrant transcription factor. This is the first report of PAX5 rearrangement in a human malignancy resulting in a chimeric transcript.
authors.affiliation: Clinica Pediatrica, Università di Milano-Bicocca, Ospedale San Gerardo, 20052 Monza, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Cazzaniga
authors.forename: M
authors.initials: M
authors.lastname: Daniotti
authors.forename: S
authors.initials: S
authors.lastname: Tosi
authors.forename: G
authors.initials: G
authors.lastname: Giudici
authors.forename: A
authors.initials: A
authors.lastname: Aloisi
authors.forename: E
authors.initials: E
authors.lastname: Pogliani
authors.forename: L
authors.initials: L
authors.lastname: Kearney
authors.forename: A
authors.initials: A
authors.lastname: Biondi
mesh_terms: D001483:Base Sequence; D015152:Blotting, Northern; D002881:Chromosomes, Human, Pair 12; D002899:Chromosomes, Human, Pair 9; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D051757:PAX5 Transcription Factor; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011506:Proteins / 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; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D004268:DNA-Binding Proteins; D051757:PAX5 Transcription Factor; D011506:Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D014157:Transcription Factors; D000097764:ETS Translocation Variant 6 Protein; C497281:PAX5 protein, human