RG Bach: Research group Molecular leukemogenesis

Medicine 5

Head of Department:
Prof. Dr. med. Andreas Mackensen

Staff: Dr. rer. nat. Christian Bach (PI), Magdalena Esser (BTA)

Research focus

Leukemia arises from normal blood cells with acquired genetic alterations which enable these cells to proliferate uncontrollably. Our goal is to uncover the downstream molecular processes initiated by those mutations that ultimately induce leukemogenesis.

Specifically, the focus of our research efforts is the HOXA9 protein, which is hyperactive in highly aggressive leukemias in children and adults. Employing both in vitro and in vivo models, we study the effects of HOXA9 hyperactivation on essential cellular processes like differentiation, proliferation, apoptosis, and cellular metabolism and how those altered processes in turn influence leukemogenesis.

Currently, we focus particularly on the impact of HOXA9 activation on posttranscriptional control of regulators of cell cycle and metabolism in leukemic cells. We specifically abrogated posttranscriptional effects of the HOXA9 protein by introduction of genetic alterations. Importantly, this alteration led to significantly less aggressive leukemia development in vivo. Moreover, we demonstrated that therapeutic inhibition of posttranscriptional regulation slows down leukemic growth considerably. Now, we analyze which target genes are regulated by HOXA9 on the posttranscriptional level and how those targets influence leukemogenesis.

In summary, the goal of our research group is to contribute to understanding the molecular processes involved in the malignant transformation of normal blood cells, ultimately resulting in novel treatment options for leukemia patients.

Current projects

  1. Post-transcriptional regulation by HOXA9
  2. Regulation of cellular metabolism by HOXA9 

Methods:

  • mouse models
  • protein-protein interaction (Co-IP, Proximity Ligation Assay)
  • protein-nucleic acid interactions (ChiP, RIP, CLIP, EMSA)
  • cell fractionation
  • flow cytometry

Collaborations:

Daniel G. Tenen, Harvard Medical School, Boston, USA
Katherine Borden, Université de Montreal, Montreal , Kanada
Sophia Adamia, Dana-Farber Cancer Institute, Boston, USA
Kathrin Renner-Sattler, Universitätsklinikum Regensburg
Heiko Bruns, Medizinische Klinik 5
Robert Slany, Lehrstuhl für Genetik

Funding:

  • Interdisziplinäres Zentrum für klinische Forschung (IZKF)
  • Deutsche Forschungsgemeinschaft (DFG)

Selected publications:

Ye M, Zhang H, Yang H, Koche R, Staber PB, Cusan M, Levantini E, Welner RS, Bach CS, Zhang J, Krivtsov A, Armstrong SA, Tenen DG. Hematopoietic differentiation is required for initiation of acute myeloid leukemia. Cell Stem Cell 2015, Nov 5;17(5):611-23.

Bach C, Slany RK. DOTting the Path to Doom: How Acceleration of Histone Methylation Leads to Leukemia. Cancer Cell 2014, Dec 8;26(6):781-2.

Bach C, Buhl S, Mueller D, García-Cuéllar MP, Maethner E, Slany RK. Leukemogenic transformation by HOXA cluster genes. Blood 2010, Apr 8;115(14):2910-8. 

Hess JL, Bittner CB, Zeisig DT, Bach C, Fuchs U, Borkhardt A, Frampton J, Slany RK. c-Myb is an essential downstream target for homeobox-mediated transformation of hematopoietic cells. Blood 2006, Jul 1;108(1):297-304.

 
 
 
 
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Summary