STEMAPL

APL a model for oncogene-targeted leukemia cure

Coordinatore	INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	France [FR]
Totale costo	2˙500˙000 €
EC contributo	2˙500˙000 €
Programma	FP7-IDEAS-ERC Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	ERC-2010-AdG_20100317
Funding Scheme	ERC-AG
Anno di inizio	2011
Periodo (anno-mese-giorno)	2011-07-01   -   2017-06-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	American University of Beirut  Organization address address: BLISS STREET city: BEIRUT postcode: 1107 2020 contact info Titolo: Dr. Nome: Fadia Cognome: Homeidan Email: send email Telefono: 96113500000000	LB (BEIRUT)	beneficiary	210˙067.15
2	INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)  Organization address address: 101 Rue de Tolbiac city: PARIS postcode: 75654 contact info Titolo: Ms. Nome: Dina Cognome: Falkenreck Email: send email Telefono: +33 1 43 62 27 19 Fax: +33 1 43 62 27 01	FR (PARIS)	hostInstitution	2˙289˙932.85
3	INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)  Organization address address: 101 Rue de Tolbiac city: PARIS postcode: 75654 contact info Titolo: Prof. Nome: "Hugues, Marie, François" Cognome: Blaudin De Thé Email: send email Telefono: +33 1 57 27 67 70 Fax: +33 1 57 27 67 95	FR (PARIS)	hostInstitution	2˙289˙932.85

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 Obiettivo del progetto (Objective)

'Acute promyelocytic leukaemia, APL, is probably one of the best-understood malignancies and the only one where highly efficient oncogene-targeted therapies (retinoic acid and arsenic) actually cure the disease. Our recent studies have addressed the molecular basis for transformation and demonstrated the essential role of sumoylation of the PML moiety of PML/RARA, relaxed DNA-binding specificity, binding to RXRA, for both transcriptional repression and transformation in primary cells, uncovering an unexpected level of complexity for in vivo transformation. We have also explored PML nuclear bodies (NB) formation, enigmatic structures that are disrupted by PML/RARA expression, restored by either RA or arsenic and may thus contribute to transformation/response. Exploring the actual basis for therapy response, we have provide some evidence that PML/RARA degradation and loss of leukaemia-initiating cells, rather than differentiation, is key to APL clearance. We propose to address the following issues: i) genetically uncouple differentiation from APL eradication ii) model transformation and therapy response iii) analyse the regulation and role of PML NBs iv) explore other models where degradation of the driving oncogene may eradicate the disease through loss of LIC activity. These studies should not only provide a complete model for APL pathogenesis and treatment response, but also open new avenues in the field of PML nuclear body biogenesis and function, as well as transcriptional activation/degradation coupling. The proposed research could provide generally applicable strategies for a variety of malignancies that are similarly driven by fusion proteins. As previously, in the APL and Adult T cell leukaemia models, our studies could also yield new directly clinically applicable therapeutic strategies.'