Truncated AML1 proteins are predicted to be expressed from out-of-frame AML1 transcripts present in myeloid leukemia cells harboring t(8;21) and t(3;21). To test whether these proteins, consisting of almost exclusively an N-terminal AML1 DNA-binding domain, interfere with myeloid differentiation we expressed a similar truncated AML1 protein in 32D cl3 myeloid cells. In all clones examined, the ectopically expressed truncated AML1 protein prevented binding of endogenous PEBP2/CBFs to DNA, possibly by interacting with all available CBF beta subunits. However, compared to control clones, the 32D cl3 clones expressing truncated AML1 remained IL-3 dependent for survival, proliferated similarly in low and high concentrations of IL-3, and differentiated similarly upon transfer to G-CSF. Thus, truncated AML1 proteins may contribute to myeloid leukemogeneis by inhibiting PEBP2/CBF activities, although contributions from other oncoproteins are likely required as well.
|Titolo:||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|
SACCHI, NICOLETTA (Secondo)
|Parole Chiave:||AML1; Differentiation; Leukemia; Myeloid|
|Settore Scientifico Disciplinare:||Settore BIO/11 - Biologia Molecolare|
|Data di pubblicazione:||giu-1996|
|Appare nelle tipologie:||01 - Articolo su periodico|