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New therapies for myeloproliferative diseases based on multi-stage and -system analyses of the haematopoietic stem-cell niche

Objective

Blood cells are produced in the bone marrow, which contains two distinct adult stem cell types: haematopoietic stem cells (HSCs), that generate all blood and immune cells, and mesenchymal stem cells (MSCs), thought to form the skeleton. HSCs traffic between bone marrow and circulation, what allows for life-saving clinical transplantation. Our previous work has shown that HSC numbers in blood are regulated by the central pacemaker in the brain, which reaches bone marrow nestin+ MSCs through the nerves. Contrarily to what it was believed, our recent data suggest that HSC-niche MSCs are different from those that form the skeleton and share instead a common origin with peripheral nerves and supporting glial cells. Thus, tight regulation of the bone marrow stem-cell niche in vertebrates might build upon developmental relationships of its cellular components. Moreover, we have shown that damage to this regulatory network is essential for the manifestation of myeloproliferative neoplasms, diseases that were previously thought to be driven solely by mutated HSCs. Also, JAK inhibitors (blocking the most frequent HSC mutation found in myeloproliferative neoplasms) cannot eradicate leukaemia stem cells. Our recent data has uncovered a selective regulation of normal and leukaemic haematopoietic progenitor maintenance, survival and division by sex hormones (oestrogens). These results might explain gender differences in blood cancer incidence and they also offer a new way of targeting leukaemia stem cells with clinically approved drugs. Nevertheless, we anticipate that the ideal future treatment of myeloproliferative diseases should target both leukaemia stem cells and their microenvironment. We have shown that protection or rescue of the niche is able to control the expansion of mutated cells. We aim to study this novel neuroendocrine regulation of bone marrow stem cells that will potentially fructify in new therapies for incurable myeloproliferative diseases.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-COG - Consolidator Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2014-CoG

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Host institution

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 594 500,00
Address
TRINITY LANE THE OLD SCHOOLS
CB2 1TN Cambridge
United Kingdom

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Region
East of England East Anglia Cambridgeshire CC
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 594 500,00

Beneficiaries (1)

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