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.

Further Reading:

·         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

·         DKFZ Press Release

Graphical abstract describing the function of BENC in normal haematopoesis and in Leukemia.

HI-STEM Mini-Symposium on Normal and Malignant Hematopoietic Stem Cells on August 28
 
The topic of the symposium will be normal and malignant hematopoietic stem cells, and there will be three talks of 30 minutes each from the following international speakers:
 
Dr. Steven Sykes, Fox Chase Comprehensive Cancer Center, Philadelphia, USA
“Mitochondrial redox biology: a therapeutic vulnerability in leukemia.”
 
Dr. Marie-Dominique Filippi, Cincinnati Children’s Hospital Medical Center, USA.
“Hematopoietic stem cell regeneration; it’s all about the mitochondria.”
 
Dr. Steven Lane, Queensland Institute for Medical Research, Brisbane, Australia.
"The role of Dnmt3a in advanced myeloproliferative neoplasm."
 
The symposium will take place on Monday August 28th at 3pm in the ZMBH, ground floor seminar room (Im Neuenheimer Feld 282).
 
For questions or contact to the speakers, please contact Dr. Michael D. Milsom (This email address is being protected from spambots. You need JavaScript enabled to view it.).

In the new paper published online at nature.com on November 8, we describe how high levels of the BCAT1 enzyme in leukemia stem can lead to DNA hypermethylation and detrimental effects in cancer cells. The work, which is based on a close cooperation with group of Bernhard Radlwimmer also at the DKFZ, opens up new options for therapy via a blockade of BCAT1. Within HI-STEM, the PhD Students Simon Raffel and Mattia Falcone are together with Niclas Kneisel from the Radlwimmer team the first authors of this study.

Further Reading:

·         Read the paper online at Nature.com:
Raffel, S., Falcone, M., Kneisel, N., Hansson, J., Wang, W., Lutz, C., Bullinger, L., Poschet, G., Nonnenmacher, Y., Barnert, A., Bahr, C., Zeisberger, P., Przybylla, A., Sohn, M., Tönjes, M., Erez, A., Adler, L., Jensen, P., Scholl, C., Fröhling, S., Cocciardi, S., Wuchter, P., Thiede, C., Flörcken, A., Westermann, J., Ehninger, G., Lichter, P., Hiller, K., Hell, R., Herrmann, C., Ho, A.D., Krijgsveld, J., Radlwimmer, B., & Trumpp, A. (2017). BCAT1 restrictsαKG levels in AML stem cells leading to IDHmut-like DNA hypermethylation. Nature, advance online publication. doi: 10.1038/nature24294

·         DKFZ Press Release (English/ Deutsch)

 

Blood cancer is initiated by leukemic stem cells characterized by a specific protein expression pattern.

Prince William and his wife, Duchess Catherine, visited the HI-STEM laboratory on July 20, 2017
As part of their official visit to Germany, Prince William and his wife, Duchess Catherine, visited the HI-STEM laboratory on July 20, 2017. Here, HI-STEM group leader Mick Milsom had the chance to introduce them into latest results of his group. The visit was part of a tour through the DKFZ, which was the first stop of the royal visit to Heidelberg.
During the visit, Milsom explained to the royal couple how a misdirected gene in blood stem cells can cause a particularly aggressive form of blood cancer. “The Duchess and the Duke were very interested in how our work relates to the development of new therapies for cancer patients and asked a number of great questions about this.” says Milsom.
“The visit was a great honor for the whole HI-STEM team and will be remembered for a long time by all of us.” says Andreas Trumpp, the managing director of HI-STEM.
 
 
  • Hematopoiesis
  • Kate Microscope
  • William Microscope
  • Explaining Microscope
  • Mick describes the normal hematopoietic system to the Duke and Duchess, and explains how this is perturbed in the setting of leukemia.
  • The Duchess of Cambridge looks at colonies formed by leukemic cells under the microscope.
  • The Duke of Cambridge looks at colonies formed by leukemic cells under the microscope.
  • Mick fields a question from the Duke of Cambridge.
  1. New study published in Nature Cell Biology
  2. HI-STEM group leader receives David B. Frohnmayer Award.
  3. Mechanism of therapy resistance in pancreatic cancer uncovered
  4. Oncogene controls stem cells during pregnancy – HI-STEM Paper featured as cover story in Cell
  5. HI-STEM scientist’s work recognized with DKFZ award
  6. Andreas Trumpp featured in GSCN Video Clip on Stem Cell Research

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