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

The Ets variant gene 6 (ETV6/TEL) gene is rearranged in the majority of pat ients with 12p13 translocations fused to a number of different partners. We present here a case of acute myeloid leukemia M4 with eosinophilia (AML-M4 Eo) positive for the CBFb/MYH11 rearrangement and carrying a t(1;12)(q25;p1 3) 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, res ulting in a chimeric protein consisting of the HLH oligomerization domain o f 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 low er 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. (C) 199 9 by The American Society of Hematology.