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- Title
CEBPA-dependent HK3 and KLF5 expression in primary AML and during AML differentiation.
- Authors
Federzoni, Elena A.; Humbert, Magali; Torbett, Bruce E.; Behre, Gerhard; Fey, Martin F.; Tschan, Mario P.
- Abstract
The basic leucine zipper transcription factor CCAAT/enhancer binding protein alpha (CEBPA) codes for a critical regulator during neutrophil differentiation. Aberrant expression or function of this protein contributes to the development of acute myeloid leukemia (AML). In this study, we identified two novel unrelated CEBPA target genes, the glycolytic enzyme hexokinase 3 (HK3) and the kru'ppel-like factor 5 (KLF5) transcription factor, by comparing gene profiles in two cohorts of CEBPA wild-type and mutant AML patients. In addition, we found CEBPA-dependent activation of HK3 and KLF5 transcription during all-trans retinoic acid (ATRA) mediated neutrophil differentiation of acute promyelocytic leukemia (APL) cells. Moreover, we observed direct regulation of HK3 by CEBPA, whereas our data suggest an indirect regulation of KLF5 by this transcription factor. Altogether, our data provide an explanation for low HK3 and KLF5 expression in particular AML subtype and establish these genes as novel CEBPA targets during neutrophil differentiation.
- Subjects
CARRIER proteins; ACUTE myeloid leukemia; NEUTROPHILS; GLUCOKINASE; KRUPPEL-like factors; TRETINOIN; GENETICS
- Publication
Scientific Reports, 2014, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/srep04261