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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 €

0

EC-Contrib. €

0

Partnership

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 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.

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

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.
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 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 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

year authors and title journal last update
List of publications.
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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