In the publication, which appeared online at Nature.comon January 17, 2018, the regulation of Myc by a modular gene enhancer in the normal hematopoietic system and in leukemia is described. The study, which was driven forward by Carsten Bahr, PhD Student at DKFZ and HI-STEM, Lisa von Paleske, former PhD student and Postdoc in the Trumpp lab and Veli Uslu from the group of François Spitz at EMBL, shows that the expression of the Myc oncogene is determined by a distant section of DNA that contains a cluster of transcriptional enhancers. In leukemia stem cells this cluster, which was named BENC for Blood Enhancer Cluster, is deregulated, which affects Myc activity and thereby accelerates cancer growth. Furthermore, it could be shown that BENC activity correlates with acute myeloid leukemia (AML) patient survival.
· Carsten Bahr*, Lisa von Paleske*, Veli V. Uslu*, Silvia Remeseiro, Naoya Takayama, Stanley W. Ng, Alex Murison, Katja Langenfeld, Massimo Petretich, Roberta Scognamiglio, Petra Zeisberger, Amelie Benk, Ido Amit, Peter W. Zandstra, Mathieu Lupien, John E. Dick, Andreas Trumpp@ and François Spitz@: A cluster of distal Myc enhancers regulates normal and leukaemic haematopoietic stem cell hierarchies. Nature 2018, DOI: 10.1038/nature25193
*: shared first authorship, @: joint corresponding authorship
Graphical abstract describing the function of BENC in normal haematopoesis and in Leukemia.