A new ETV6/TEL partner gene, ARG (ABL-related gene or ABL2), identified in an AML-M3 cell line with a t(1;12)(q25;p13) translocation.
The ETV6/TEL gene has been reported to fuse to PDGFRbetab MDS1/EVI1, BTL, ACS2, STL, JAK2, ABL, CDX2, TRKC, AML1, and MN1. Among them, PDGFRbeta, ABL, JAK2, and TRKC are tyrosine kinases (TK). We identified a novel ETV6 partner gene, ARG (ABL-related gene or ABL2), another TK gene in a cell line established from a patient with acute myelogenous leukemia (AML-M3) with a t(15;17)(q22;q11.2) and a t(1;12)(q25;p13), which has the remarkable feature to differentiate to mature eosinophils in culture with all-trans retinoic acid and cytokines. The ETV6/ARG transcripts consisted of exon 1 to 5 of ETV6 and the 3' portion of ARG starting from exon 1B or exon 2, resulting in an open reading frame for a fusion protein consisting of the entire PNT oligomerization domain of ETV6 and all of the functional domains of ARG including the TK domain. This is the same protein structure as identified in the other ETV6 TK fusion proteins. The reciprocal ARG/ETV6 transcript was not expressed, and the normal ETV6 allele was not deleted or rearranged. Although the ABL is known to be involved in various human malignancies, ARG has not been involved in human malignancies despite its high homology to ABL. Thus, this is the first report showing involvement of ARG in human leukemia. The ETV6/ARG protein may be involved in the unique differentiation capacity of this cell line. (Blood. 2000;95:2126-2131)
Iijima
Y
Y
Division of Molecular Cytogenetics, Department of Clinical Pathology, Research Institute, International Medical Center of Japan, Tokyo, Japan.
Ito
T
T
Oikawa
T
T
Eguchi
M
M
Eguchi-Ishimae
M
M
Kamada
N
N
Kishi
K
K
Asano
S
S
Sakaki
Y
Y
Sato
Y
Y
D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D015152:Blotting, Northern; D015139:Blotting, Southern; D002878:Chromosomes, Human, Pair 1; D002881:Chromosomes, Human, Pair 12; D004268:DNA-Binding Proteins / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics*; D008297:Male; D008957:Models, Genetic; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D050783:Proto-Oncogene Proteins c-ets; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured; D000097764:ETS Translocation Variant 6 Protein
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D015514:Oncogene Proteins, Fusion; D011505:Protein-Tyrosine Kinases; D050783:Proto-Oncogene Proteins c-ets; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D000097764:ETS Translocation Variant 6 Protein; C490755:SORBS2 protein, human