A new ETV6/TEL partner gene, ARG (ABL-related gene or ABL2), identified inan AML-M3 cell line with a t(1;12)(q25;p13) translocation

The ETV6/TEL gene has been reported to fuse to PDGFR beta b MDS1/EVI1, BTL, ACS2, STL, JAK2, ASL, CDX2, TRKC, AML1, and MN1. Among them, PDGFR beta, A SL, JAK2, and TRKC are tyrosine kinases (TK), We identified a novel ETV6 pa rtner gene, ARG (ABL-related gene or ASL2), another TK gene in a cell line established from a patient with acute myelogenous leukemia (AML-MB) with a t(15;17)(q22;q11.2) and a t(1;12)(q25;p13), which has the remarkable featur e 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 E TV6 and the 3' portion of ARG starting from exon IB or exon 2, resulting in an open reading frame for a fusion protein consisting of the entire PNT ol igomerization domain of ETV6 and all of the functional domains of ARG inclu ding 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. Althou gh the ABL Is known to be involved in various human malignancies, ARG has n ot been involved in human malignancies despite its high homology to ASL, Th us, 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. (C) 2000 by The American Society of Hematology.