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Project leader:  

Ekaterina Bulycheva
Ärztin in Weiterbildung
Medizinische Klinik und Poliklinik I
Universitätsklinikum Carl Gustav Carus
der Technischen Universität Dresden
Fetscherstraße 74
01307 Dresden

Project title:   

Signaling pathways employed by erythropoietin to control the osteo-hematopoietic niche of patients with myelodysplastic syndromes (MDS)

Involved SFB members (co-leaders):    

Prof. Dr. Uwe Platzbecker
Medizinische Klinik und Poliklinik I
Universitätsklinikum Carl Gustav Carus
der Technischen Universität Dresden
SFB-Teilprojekt B13

Prof. Dr. Lorenz Hofbauer
Medizinische Klinik und Poliklinik III
Universitätsklinikum Carl Gustav Carus
der Technischen Universität Dresden
SFB-Teilprojekt B13

Funding period:   

01.10.14 – 30.09.15

Abstract:   

Myelodysplastic syndromes (MDS) represent heterogeneous clonal disorders of hematopoietic stem/progenitor cells (HSPCs) and possibly their niche. Most patients become red blood cell transfusion-dependent during the course of their disease followed by a concomitant and often excessive elevation of serum erythropoietin (EPO) levels. The pathophysiological events occurring in MDS are still poorly defined. However, distinct molecular and cytogenetic aberrations have been described in HSPCs along with alterations of the bone marrow microenvironment and the immune system. The bone microenvironment, including osteoblasts (OBs, derived from mesenchymal stem cells), osteoclasts (OCs) and macrophages (both derived from HSPCs), is involved in supporting and regulating the complex processes of hematopoiesis. Despite the critical role in regulating HSPC function and differentiation its role in modulating hematopoietic cells in MDS remains unknown and it is unclear, how exogenous factors such as EPO alter the properties of the bone marrow niche. Therefore, we will test the hypothesis, whether the cellular components of the HSPC niche and their function are specifically altered in MDS, and whether the niche function could be modulated by EPO. The goal of this study is to gain insight into the cellular and molecular basis of disturbed crosstalk in the bone marrow of patients with MDS and to propose possible clinically relevant ways of therapeutic intervention to reconstitute it.

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Relevant publications:  
  1. Bulycheva E, Rauner M, Medyouf H, Theurl I, Bornhäuser M, Hofbauer LC, Platzbecker U. Myelodysplasia is in the niche: novel concepts and emerging therapies. Leukemia (2014), in press. doi: 10.1038/leu.2014.325
  2.  Ferrer RA, Wobus M, List C, Wehner R, Schönefeldt C, Brocard B, et al. Mesenchymal stromal cells from patients with myelodysplastic syndrome display distinct functional alterations that are modulated by lenalidomide. Haematologica (2013); 98(11): 1677-85.
  3. Medyouf H, Mossner M, Jann JC, Nolte F, Raffel S, Herrmann C, et al. Myelodysplastic cells in patients reprogram mesenchymal stromal cells to establish a transplantable stem cell niche disease unit. Cell Stem Cell (2014); 14(6): 824-37.

 

 

 

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Funding program:

DFG