DNA-BINDING DOMAIN OF AML1, EXPRESSED IN T(8-21) AND T(3-21) MYELOID LEUKEMIAS, INHIBITS PEBP2 CBF DNA-BINDING BUT IS NOT SUFFICIENT TO TRANSFORM 32D CL3 MYELOID CELLS/

Truncated AML1 proteins are predicted to be expressed from out-of-fram e AML1 transcripts present in myeloid leukemia cells harboring t(8;21) and t(3;21). To test whether these proteins, consisting of almost exc lusively an N-terminal AML1 DNA-binding domain, interfere with myeloid differentiation we expressed a similar trunctated AML1 protein in 32D cI3 myeloid cells. In all clones examined, the ectopically expressed truncated AML1 protein prevented binding of endogenous PEBP2/CBFs to D NA, possibly by interacting with all available CBF beta subunits. Howe ver, compared to control clones, the 32D cI3 clones expressing truncat ed AML1 remained IL-3 dependent for survival, proliferated similarly i n low and high concentrations of IL-3, and differentiated similarly up on transfer to G-CSF. Thus, truncated AML1 proteins may contribute to myeloid leukemogenesis by inhibiting PEBP2/CBF activities, although co ntributions from other oncoproteins are likely required as well.