title: The tyrosine kinase abl-related gene ARG is fused to ETV6 in an AML-M4Eo patient with a t(1;12)(q25;p13): molecular cloning of both reciprocal transcripts.
abstract: The Ets variant gene 6 (ETV6/TEL) gene is rearranged in the majority of patients with 12p13 translocations fused to a number of different partners. We present here a case of acute myeloid leukemia M4 with eosinophilia (AML-M4Eo) positive for the CBFb/MYH11 rearrangement and carrying a t(1;12)(q25;p13) that involves the ETV6 gene at 12p13. By 3'rapid amplification of cDNA ends-polymerase chain reaction (3'RACE-PCR), a novel fusion transcript was identified between the ETV6 and the Abelson-related gene (ARG) at 1q25, resulting in a chimeric protein consisting of the HLH oligomerization domain of ETV6 and the SH2, SH3, and protein tyrosine kinase (PTK) domains of ARG. The reciprocal transcript ARG-ETV6 was also detected in the patient RNA by reverse transcriptase-polymerase chain reaction (RT-PCR), although at a lower expression level. The ARG gene encodes for a nonreceptor tyrosine kinase characterized by high homology with c-Abl in the TK, SH2, and SH3 domains. This is the first report on ARG involvement in a human malignancy.
authors.affiliation: Clinica Pediatrica Università di Milano-Bicocca, Ospedale San Gerardo, Monza, Italy. fondazione.tettamanti@galactica.it
authors.forename: G
authors.initials: G
authors.lastname: Cazzaniga
authors.forename: S
authors.initials: S
authors.lastname: Tosi
authors.forename: A
authors.initials: A
authors.lastname: Aloisi
authors.forename: G
authors.initials: G
authors.lastname: Giudici
authors.forename: M
authors.initials: M
authors.lastname: Daniotti
authors.forename: P
authors.initials: P
authors.lastname: Pioltelli
authors.forename: L
authors.initials: L
authors.lastname: Kearney
authors.forename: A
authors.initials: A
authors.lastname: Biondi
mesh_terms: D002878:Chromosomes, Human, Pair 1; D002881:Chromosomes, Human, Pair 12; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D016313:Genes, abl; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D004268:DNA-Binding Proteins; D015514:Oncogene Proteins, Fusion; D011505:Protein-Tyrosine Kinases; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D014157:Transcription Factors; D000097764:ETS Translocation Variant 6 Protein