Objective
Background: Altered high-density lipoprotein (HDL)-cholesterol homeostasis has been observed in hematologic malignancies but genetic evidences proving causality have been lacking. The ability of HDL to promote cholesterol efflux depends on two ATP-binding cassette transporters ABCA1 and ABCG1, which exhibit anti-myeloproliferative activity in preclinical mouse models.
Hypothesis: Somatic mutations in ABCA1 and ABCG1 may be observed in myeloproliferative disorders and could be functionally inactive disabling both cholesterol efflux and anti-tumor activity.
Preliminary data: Five new somatic mutations in ABCA1 were identified out of 26 tumor samples from patients with chronic myelomonocytic leukaemia (CMML) with an unexpected frequency of 19% and conferred a proliferative advantage when transfected into HEK293 cells.
Aims: The aim of this study is to 1) test the functional relevance of newly identified ABCA1 mutants on myeloproliferative diseases and 2) apprehend the molecular mechanisms that could provide a proliferative advantage to these mutants.
Methods: We will take advantage of the generation of these mutants to test their relevance (Aim. 1) and mechanisms of action (Aim. 2) both in vitro in relevant myeloblast cell lines and in vivo by performing a transplantation of bone marrow cells transduced with these mutants.
Keywords: Leukaemia, HDL cholesterol, ATP-binding cassette transporters, human somatic mutations
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.
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine transplantation
- medical and health sciences clinical medicine oncology leukemia
- medical and health sciences basic medicine physiology homeostasis
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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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.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2013-CIG
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Funding Scheme
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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.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
75654 PARIS
France
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