title: CEBPA-dependent HK3 and KLF5 expression in primary AML and during AML differentiation.
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 krüppel-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.
authors.affiliation: 1] Experimental Oncology/Hematology, Department of Clinical Research, University of Bern, Bern, Switzerland [2] Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland [3] Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA [4].
authors.forename: Elena A
authors.initials: EA
authors.lastname: Federzoni
authors.affiliation: 1] Experimental Oncology/Hematology, Department of Clinical Research, University of Bern, Bern, Switzerland [2] Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland [3].
authors.forename: Magali
authors.initials: M
authors.lastname: Humbert
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Torbett
authors.affiliation: Department for Hematology and Oncology, University Hospital of Leipzig, Leipzig, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Behre
authors.affiliation: 1] Experimental Oncology/Hematology, Department of Clinical Research, University of Bern, Bern, Switzerland [2] Department of Medical Oncology, Inselspital, Bern University Hospital, Bern, Switzerland.
authors.forename: Martin F
authors.initials: MF
authors.lastname: Fey
authors.affiliation: 1] Experimental Oncology/Hematology, Department of Clinical Research, University of Bern, Bern, Switzerland [2] Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland [3] Department of Medical Oncology, Inselspital, Bern University Hospital, Bern, Switzerland [4] Division of Experimental Pathology, Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: Mario P
authors.initials: MP
authors.lastname: Tschan
mesh_terms: D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D006593:Hexokinase / Q000378:metabolism*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology*; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology*
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; C492214:KLF5 protein, human; D051741:Kruppel-Like Transcription Factors; D006593:Hexokinase