Myeloid transformation by MLL-ENL depends strictly on C/EBP
Wesolowski R, Kowenz-Leutz E, Zimmermann K, Dörr D, Hofstätter M, Slany R, Mildner A, Leutz A (2021)
Publication Type: Journal article
Publication year: 2021
Journal
Book Volume: 4
Journal Issue: 1
Abstract
Chromosomal rearrangements of the mixed-lineage leukemia gene MLL1 are the hallmark of infant acute leukemia. The granulocyte-macrophage progenitor state forms the epigenetic basis for myelomonocytic leukemia stemness and transformation by MLL-type oncoproteins. Previously, it was shown that the establishment of murine myelomonocytic MLL-ENL transformation, but not its maintenance, depends on the transcription factor C/EBPα, suggesting an epigenetic hit-and-run mechanism of MLL-driven oncogenesis. Here, we demonstrate that compound deletion of Cebpa/Cebpb almost entirely abrogated the growth and survival of MLL-ENL-transformed cells. Rare, slow-growing, and apoptosis-prone MLL-ENL-transformed escapees were recovered from compound Cebpa/Cebpb deletions. The escapees were uniformly characterized by high expression of the resident Cebpe gene, suggesting inferior functional compensation of C/EBPα/C/EBPβ deficiency by C/EBPε. Complementation was augmented by ectopic C/EBPβ expression and downstream activation of IGF1 that enhanced growth. Cebpe gene inactivation was accomplished only in the presence of complementing C/EBPβ, but not in its absence, confirming the Cebpe dependency of the Cebpa/Cebpb double knockouts. Our data show that MLL-transformed myeloid cells are dependent on C/EBPs during the initiation and maintenance of transformation.
Authors with CRIS profile
Involved external institutions
Germany (DE)How to cite
APA:
Wesolowski, R., Kowenz-Leutz, E., Zimmermann, K., Dörr, D., Hofstätter, M., Slany, R.,... Leutz, A. (2021). Myeloid transformation by MLL-ENL depends strictly on C/EBP. Life Science Alliance, 4(1). https://dx.doi.org/10.26508/lsa.202000709
MLA:
Wesolowski, Radoslaw, et al. "Myeloid transformation by MLL-ENL depends strictly on C/EBP." Life Science Alliance 4.1 (2021).
BibTeX: Download