CEBPA-dependent HK3 and KLF5 expression in primary AML and during AML differentiation

Elena A Federzoni; Magali Humbert; Bruce E Torbett; Gerhard Behre; Martin F Fey; Mario P Tschan

doi:10.1038/srep04261

CEBPA-dependent HK3 and KLF5 expression in primary AML and during AML differentiation

Sci Rep. 2014 Mar 3:4:4261. doi: 10.1038/srep04261.

Authors

Elena A Federzoni¹, Magali Humbert², Bruce E Torbett³, Gerhard Behre⁴, Martin F Fey⁵, Mario P Tschan⁶

Affiliations

¹ 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].
² 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].
³ Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA.
⁴ Department for Hematology and Oncology, University Hospital of Leipzig, Leipzig, Germany.
⁵ 1] Experimental Oncology/Hematology, Department of Clinical Research, University of Bern, Bern, Switzerland [2] Department of Medical Oncology, Inselspital, Bern University Hospital, Bern, Switzerland.
⁶ 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.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

CCAAT-Enhancer-Binding Proteins / metabolism*
Cell Differentiation
Cell Line, Tumor
Cell Transformation, Neoplastic / metabolism
Cell Transformation, Neoplastic / pathology
Hexokinase / metabolism*
Humans
Kruppel-Like Transcription Factors / metabolism*
Leukemia, Myeloid, Acute / metabolism*
Leukemia, Myeloid, Acute / pathology*
Neutrophils / metabolism*
Neutrophils / pathology*

Substances

CCAAT-Enhancer-Binding Proteins
CEBPA protein, human
KLF5 protein, human
Kruppel-Like Transcription Factors
Hexokinase

Abstract

Publication types

MeSH terms

Substances

Grants and funding