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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.

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

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 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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