Implication of TEL-derived proteins in oncogenesis

TEL is a gene of the ETS family which is frequently altered in human leukemia as the result of specific chromosomal translocations. The TEL protein has features which distinguish it from other members of the ETS family. First, unlike most other ETS proteins, TEL is a sequence-specific transcriptional repressor. Second, TEL self-associates to form homotypic oligomers, a property which is important for its trans-repressing properties. The chromosomal translocations which affect TEL in leukemia generate fusion proteins. These can be grouped into two major categories. The first comprises chimeric proteins in which the amino-terminal region of TEL (including its self-association domain) is fused to the catalytic domain of protein tyrosine kinases (PDGFRbeta ; ABL ; JAK2 ; TRKC). The second includes fusion proteins between TEL and other transcriptional regulators (AML1 ; MN1). The latter can either maintain (TEL-MN1 fusions) or not maintain (TEL-AML1) the DNA binding domain (ETS domain) of TEL. Although deregulating different intracellular signaling pathways, these fusion proteins all appear to activate their oncogenic properties by using and subverting from their normal function several remarkable functional domains of TEL. The increasing number of chromosomal translocations affecting TEL, most often in leukemia, the diversity of the partners involved in these translocations and the presumed role of the loss of the non rearranged TEL allele in B-ALL with t(12 ; 21), clearly point to TEL as an important target in oncogenic processes.