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EU-Förderung (171.473 €): Inhibitor von DUX4-IGH zur Beseitigung akuter lymphatischer Leukämie Hor27.04.2019 EU-Rahmenprogramm für Forschung und Innovation "Horizont"
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Inhibitor von DUX4-IGH zur Beseitigung akuter lymphatischer Leukämie
The second most important cause of death and morbidity in Europe is cancer and B-cell acute lymphoblastic leukaemia (B-ALL) is the most common paediatric cancer and cause of cancer-related death before 20 years. In up to 7% of cases, the disease is caused by rearrangements of the genetic regulator DUX4 to the IGH locus, giving rise to the DUX4-IGH fusion. While ectopic expression of DUX4 induces cell death, DUX4-IGH drives transformation. Even though the two proteins share the same DNA binding domain (dbd), DUX4 and DUX4-IGH drive the transcription of non-overlapping target genes. Through proteomics, my lab identified a specific DUX4-IGH inhibitor, which directly binds to DUX4-IGH dbd blocking the activation of target genes. Based on this evidence, the goal of IDEAL is to test the antileukemic activity of the inhibitor in pre-clinical settings. Using cellular models, I will test the ability of the inhibitor to block transformation driven by DUX4-IGH. I expect to see a significant inhibition of DUX4-IGH driven transformation in the presence of its inhibitor, associated with reduced proliferation, clonogenic and self-renewal potential. To test the efficacy of DUX4-IGH inhibition in leukemia development, I will employ animal models (murine bone marrow transplantation assays and patient derived xenografts of DUX4-IGH B-ALL) and assess disease latency in the presence or absence of the inhibitor. I predict that the inhibitor will block or significantly delay DUX4-IGH B-ALL. Pre-clinical validation of the DUX4-IGH inhibitor will help defining effective therapeutic strategies for DUX4-IGH B-ALL patients, improving clinical outcome and lowering treatment toxicity, thus overall promoting Europe's healthcare. Through IDEAL I will expand my expertise in leukaemia research and I will acquire project management and leadership abilities that will foster my personal and professional development as an independent scientist.
Geförderte Unternehmen:
| Firmenname | Förderungssumme |
| Ospedale SAN Raffaele Srl | 171.473 € |
Quelle: https://cordis.europa.eu/project/id/841957
Diese Bekanntmachung wurde von Englisch nach Deutsch übersetzt. Die Bekanntmachung bezieht sich auf einen vergangenen Zeitpunkt, und spiegelt nicht notwendigerweise den heutigen Stand wider. Der aktuelle Stand wird auf folgender Seite wiedergegeben: Ospedale SAN Raffaele Srl, Segrate, Italien.
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