Molecular cytogenetic and clinical findings in ETV6/ABL1-positive leukemia

Rearrangements of 12p, resulting from deletions or translocations, are comm on findings in hematologic malignancies. In many cases, these rearrangement s target: the ETV6 gene (previously called TEL) located at 12p13. Various p artner genes have been implicated in the formation of fusion genes with ETV 6. These include PDGFRB, JAK2, NTRK3, ABL2, and ABL1, each of which encodes for proteins with tyrosine kinase activity. To date, ETV6/ABLI transcripts have been detected in only four patients with a leukemic disorder. Here, w e describe one adult with chronic myeloid leukemia and a child with T-cell acute lymphocytic leukemia with ETV6/ABLI. Molecular cytogenetic analysis c onfirmed that formation of an ETV6/ABLI fusion in these patients required a t least three chromosomal breaks and showed that each of these translocatio ns is the result of a complex chromosomal rearrangement. Molecular analysis showed the presence of two fusion transcripts in both patients as the resu lt of alternative splicing, questioning the suggested role of these transcr ipts in the lineage specificity. Clinical findings of these patients were c ompared to those of previously reported cases, and the possible clinical an d biological similarities between ETV6/ABLI and other fusion genes leading to increased tyrosine kinase activity are discussed. (C) 2001 Wiley-Liss, I nc.