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Financement de l’UE (958 750 €) : Interaction dynamique entre la méthylation de l’ADN, les modifications des histones et l’activité des super-amplificateurs dans les lymphocytes T normaux et pendant … Hor 18/06/2015 Programme de recherche et d'innovation de l'UE « Horizon »
Vue d’ensemble
Texte
Interaction dynamique entre la méthylation de l’ADN, les modifications des histones et l’activité des super-amplificateurs dans les lymphocytes T normaux et pendant la transformation des lymphocytes T malins
Dynamic interplay between histone modifications and DNA methylation defines the chromatin structure of the humane genome and serves as a conceptual framework to understand transcriptional regulation in normal development and human disease. The ultimate goal of this research proposal is to study the chromatin architecture during normal and malignant T cell differentiation in order to define how DNA methylation drives oncogenic gene expression as a novel concept in cancer research. T-cell acute lymphoblastic leukemia (T-ALL) accounts for 15% of pediatric and 25% of adult ALL cases and was originally identified as a highly aggressive tumor entity. T-ALL therapy has been intensified leading to gradual improvements in survival. However, 20% of pediatric and 50% of adult T-ALL cases still relapse and ultimately die because of refractory disease. Research efforts have unravelled the complex genetic basis of T-ALL but failed to identify new promising targets for precision therapy. Recent studies have identified a subset of T-ALLs whose transcriptional programs resemble those of early T-cell progenitors (ETPs), myeloid precursors and hematopoietic stem cells. Importantly, these so-called ETP-ALLs are characterized by early treatment failure and an extremely poor prognosis. The unique ETP-ALL gene expression signature suggests that the epigenomic landscape in ETP-ALL is markedly different as compared to other genetic subtypes of human T-ALL. My project aims to identify genome-wide patterns of DNA methylation and histone modifications in genetic subtypes of human T-ALL as a basis for elucidating how DNA methylation drives the expression of critical oncogenes in the context of poor prognostic ETP-ALL. Given that these ETP-ALL patients completely fail current chemotherapy treatment, tackling this completely novel aspect of ETP-ALL genetics will yield new targets for therapeutic intervention in this aggressive haematological malignancy.
| Universiteit Gent | 958 750 € |
https://cordis.europa.eu/project/id/639784
Cette annonce se réfère à une date antérieure et ne reflète pas nécessairement l’état actuel. L’état actuel est présenté à la page suivante : Universiteit Gent Andere Rechtsform, 9000 Gand, Belgique.
