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Blood, Vol. 94 No. 12 (December 15), 1999:
pp. 4370-4373
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
Giovanni Cazzaniga,
Sabrina Tosi,
Alessandra Aloisi,
Giovanni Giudici,
Maria Daniotti,
Pietro Pioltelli,
Lyndal Kearney, and
Andrea Biondi
From the Clinica Pediatrica Università di Milano-Bicocca,
Ospedale San Gerardo, Monza, Italy; the MRC, Molecular Haematology
Unit, Institute of Molecular Medicine, Oxford, UK; and the Dipartimento
di Ematologia, Ospedale San Gerardo, Monza, Italy.
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.
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