Recruitment of the nuclear receptor corepressor N-CoR by the TEL moiety ofthe childhood leukemia-associated TEL-AML1 oncoprotein

The t(12;21)(p13;q22) chromosomal translocation Is the most frequent illegi timate gene recombination in a pediatric cancer and occurs in approximately 25% of common acute lymphoblastic leukemia (cALL) cases. This rearrangemen t results in the in frame fusion of the 5'-region of the ETS-related gene, TEL (ETV6), to almost the entire acute myeloid leukemia 1 (AML1) (also call ed CBFA2 or PEBP2AB1) locus and expression of the TEL-AML1 chimeric protein . Although AML1 stimulates transcription, TEL-AML1 functions as a repressor of some AML1 target genes. In contrast to the wild type AML1 protein, both TEL and TEL-AML1 interact with N-coR, a component of the nuclear receptor corepressor complex with histone deacetylase activity. The interaction betw een TEL and N-coR requires the central region of TEL, which is retained In TEL-AML1, and TEL lacking this domain is impaired in transcriptional repres sion. Taken together, our results suggest that TEL-AML1 may contribute to l eukemogenesis by recruiting N-CoR to AML1 target genes and thus imposing an altered pattern of their expression. (Blood, 2000;96:2557-2561) (C) 2000 b y The American Society of Hematology.