Project description
Chronic inflammation: can it lead to leukaemia?
Emerging evidence suggests that the microenvironment of the bone marrow may play a role in the development of haematological malignancies. In particular, chronic inflammation generates key mediators that can affect haematopoietic stem cells (HSCs), leading to exhaustion of self-renewal capacity and even leukaemia. Scientists of the EU-funded SuccHSC project aim to study the role of succinate, a major inflammation-induced effector molecule which can reach the nucleus and modify histones. Researchers will investigate the impact of succinate on histone modification and gene expression in normal and leukaemic samples, providing insight into leukaemia development.
Objective
In life, no matter how small, changes can have huge impact on its quality. For hematopoietic stem cells (HSC), similar can happen. Through minor shifts, from normal to pre-leukemic and finally leukemic phenotype, generation of leukemic stem cells (LSC) results in overt malignancy, such is acute myeloid leukemia (AML). Life quality of AML patients is severely impaired, even in “disease-free” state after the treatment. AML chemotherapy and stem cell transplant offers 5-year survival to only 20% of patients above age of sixty, 40% to the rest. Currently, a major clinical factor in AML onset and relapse are ever-present LSC. Mechanisms by which HSC turn into LSC, in their highly regulated environment, are still largely unknown, which is why new knowledge is needed to unveil this troubling issue. With the growing amount of data correlating chronic inflammation and onset of various types of malignancies, the SuccHSC project will explore the role of succinate, one of the major inflammation-induced effector molecules, in LSC formation by epigenetic remodeling of HSC. Chronic inflammation generates various molecules, which can be picked-up by bone marrow HSC. Chronic HSC activation leads to peripheral blood entering, myeloid skewing, self-renewal exaustion and even perhaps leukemia. On mechanistic side, HSC react to inflammatory mediators by elevated glycolysis, reduced oxygen and increased succinate. New succinate molecules can reach nucleus through mito-nuclear communication. Among other modifications, histones were shown to be modified with succinate, but yet with no known role. SuccHSC will explore histone succinylation and its effect on gene expression comparing leukemic and normal human samples biochemically, by ChIP-seq and by RNA-seq. Transgene succinate-dehydrogenase KO mice model, which accumulates succinate, will be used to confirm succinylation role in gene expression regulation and HSC transformation into pre-leukemic cell stage.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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.
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2020
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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.
9019 Tromso
Norway
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.