CCAAT/enhancer binding protein epsilon is a potential retinoid target gene in acute promyelocytic leukemia treatment.

摘要: The CCAAT/enhancer binding protein epsilon (C/EBPepsilon) is a nuclear transcription factor expressed predominantly in myeloid cells and implicated as potential regulator of differentiation. We show that it was rapidly induced the acute promyelocytic leukemia (APL) cell line NB4 during granulocytic differentiation after exposure to retinoic acid (RA). Our data suggest induction C/EBPepsilon expression through receptor alpha (RARalpha) pathway. Reporter gene studies showed promoter/enhancer activity increased retinoid-dependent fashion via response element (RARE) present promoter region C/EBPepsilon. RA-induced markedly U937 myelomonoblasts were express leukemia/RARalpha (PML/RARalpha), but not those zinc finger/RARalpha (PLZF/RARalpha). In retinoid-resistant APL lines, either or only at very high concentrations RA (>/=10(-6) M). addition, forced myelomonoblastic mimicked terminal differentiation, including morphologic changes, CD11b/CD66b expression, secondary granule expression. strongly downstream target responsible for cells.