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/
M. Britosbray et al., 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/, Leukemia, 10(6), 1996, pp. 984-990
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.