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HemNichMDS SIGNED

Functional and Molecular Analyses of the Interplay between Hematopoietic and Mesenchymal Niche Cells in Human Myelodysplastic Syndromes.

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

HemNichMDS project word cloud

Explore the words cloud of the HemNichMDS project. It provides you a very rough idea of what is the project "HemNichMDS" about.

hsc indicate advantage gt transplantation mesenchymal purified complications myelodysplastic educate groundbreaking hscs xenograft therapeutic perform diseased 10 transfusions strategies treatment 45 primary population elderly propensity characterization cytopenias cell functional innovative patients blood niche prevalence limited suitable stem prognostic diseases interplay molecular curative triggered outcomes leukemia translate peripheral decipher environment microenvironment patient disrupting neoplasms mice syndromes acute evolve applies vivo younger revealed clonal propagate mature mds mainly highlighting aging reinforcing abnormal secondary healthcare continuous myeloid hematopoietic rely data human heterogeneous ineffective self ing marrow lt donors model interactions deaths indicates bone cells

Project "HemNichMDS" data sheet

The following table provides information about the project.

Coordinator	CHEMOTHERAPEUTISCHES FORSCHUNGSINSTITUT GEORG-SPEYER-HAUS STIFTUNG Organization address address: PAUL EHRLICH STRASSE 42-44 city: FRANKFURT postcode: 60596 website: www.georg-speyer-haus.de contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	Germany [DE]
Total cost	1˙500˙000 €
EC max contribution	1˙500˙000 € (100%)
Programme	1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
Code Call	ERC-2014-STG
Funding Scheme	ERC-STG
Starting year	2015
Duration (year-month-day)	from 2015-08-01 to 2020-07-31

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	CHEMOTHERAPEUTISCHES FORSCHUNGSINSTITUT GEORG-SPEYER-HAUS STIFTUNG CHEMOTHERAPEUTISCHES FORSCHUNGSINSTITUT GEORG-SPEYER-HAUS STIFTUNG Organization address address: PAUL EHRLICH STRASSE 42-44 city: FRANKFURT postcode: 60596 website: www.georg-speyer-haus.de contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	DE (FRANKFURT)	coordinator	1˙500˙000.00

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Project objective

Myelodysplastic syndromes (MDS) are heterogeneous clonal hematopoietic stem cell diseases mainly affecting the elderly (45/100,000 in >70 years). The prevalence of MDS is expected to rise mainly as a result of an aging population. MDS is characterized by ineffective production of mature blood cells with peripheral cytopenias and the propensity to evolve to acute myeloid leukemia. Most MDS patients rely on continuous blood transfusions resulting in significant costs to healthcare systems and, most importantly, secondary effects leading to complications and patient deaths. The only potential curative treatment for MDS is hematopoietic stem cells (HSC) transplantation, which is limited to younger patients with suitable donors (<10% of MDS patients). Increasing evidence indicates that myeloid neoplasms can be triggered by abnormal functional properties of the bone marrow microenvironment in mice. However, it remains to be seen whether this also applies to human hematopoietic neoplasms. Our work revealed that patient-derived mesenchymal niche cells are essential to propagate human MDS HSCs in vivo, thus highlighting the crucial role of the niche in human MDS. Moreover, our data indicate that human MDS hematopoietic cells may “educate” their niche environment into a self-reinforcing one. The goal of our proposal is to decipher the interplay between hematopoietic and mesenchymal niche cells in human MDS, and to assess innovative means by which we could target diseased cells to improve MDS patient outcomes. We will perform a comprehensive molecular characterization of highly purified primary mesenchymal niche cells to define new prognostic/therapeutic niche factors in MDS. More importantly, we will take advantage of our unique xenograft model of MDS to translate our findings into groundbreaking novel therapeutic strategies for MDS patients, by disrupting essential niche/MDS stem cell interactions.

Publications

List of publications.
year	authors and title	journal	last update
2017	Hind Medyouf The microenvironment in human myeloid malignancies: emerging concepts and therapeutic implications published pages: 1617-1626, ISSN: 0006-4971, DOI: 10.1182/blood-2016-11-696070	Blood 129/12	2020-04-01
2016	M. Mossner, J.-C. Jann, J. Wittig, F. Nolte, S. Fey, V. Nowak, J. Oblander, J. Pressler, I. Palme, C. Xanthopoulos, T. Boch, G. Metzgeroth, H. Rohl, S. H. Witt, H. Dukal, C. Klein, S. Schmitt, P. Gelss, U. Platzbecker, E. Balaian, A. Fabarius, H. Blum, T. J. Schulze, M. Meggendorfer, C. Haferlach, A. Trumpp, W.-K. Hofmann, H. Medyouf, D. Nowak Mutational hierarchies in myelodysplastic syndromes dynamically adapt and evolve upon therapy response and failure published pages: 1246-1259, ISSN: 0006-4971, DOI: 10.1182/blood-2015-11-679167	Blood 128/9	2020-04-01

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