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Blood, Vol. 95 No. 6 (March 15), 2000:
pp. 2126-2131
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
Yoshimi Iijima,
Takashi Ito,
Tsuneyuki Oikawa,
Mariko Eguchi,
Minenori Eguchi-Ishimae,
Nanao Kamada,
Kenji Kishi,
Shigetaka Asano,
Yoshiyuki Sakaki, and
Yuko Sato
Division of Molecular Cytogenetics, Department of Clinical
Pathology, Research Institute, International Medical Center of Japan,
Tokyo, Japan; Human Genome Center, Institute of Medical Science,
University of Tokyo, Tokyo, Japan; Department of Cell Genetics, Sasaki
Institute; Department of Cancer Cytogenetics, Research Institute or
Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan;
Fourth Department of Internal Medicine, School of Medicine, Tokai
University; Department of Hematology/Oncology, Institute of Medical
Science, University of Tokyo, Tokyo, Japan.
The ETV6/TEL gene has been reported to fuse to
PDGFR b MDS1/EVI1, BTL, ACS2,
STL, JAK2, ABL, CDX2, TRKC,
AML1, and MN1. Among them, PDGFR,
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.
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