Project: Metabolic vulnerabilities for personalized therapeutic approaches in acute myeloid leukemia

Acronym	MEET-AML (Reference Number: ERAPERMED2019-290)
Duration	01/04/2020 - 31/03/2023
Project Topic	Current personalized medicine approaches in acute myeloid leukemia (AML) are restricted to the identification of actionable genomic lesions, with great differences in clinical outcome and response to treatment, reflecting inter-individual heterogeneity. A clear understanding of the biological consequences of the genomic alterations is crucial to tailor therapeutic strategies. Several oncogenic and tumor suppressor pathways target the metabolic network and cooperate with functionally and/or structurally altered metabolic enzymes to define the leukemic phenotype. AML cells undergo metabolic reprogramming and are sensitive to a number of metabolic inhibitors at the preclinical level. However, subgroup- and patient-specific metabolic dependencies and preferences are largely unexplored. MEET-AML aims to identify metabolic vulnerabilities in AML and develop a model to integrate multilayer omics and social data in order to define AML phenotypic profiles and personalized therapeutic approaches targeting leukemic cell metabolism, while understanding patients’ perspective. We will characterize the genomic and transcriptomic landscape of AML (WP2) and map their metabolic and proteomic networks (WP3). Patients’ preferences will be assessed by qualitative and quantitative approaches and direct involvement of patient representatives (WP6). Omics data will be integrated through Systems Biology algorithms to create a new model for definition of phenotypic profiles, prediction of synthetic lethality based on human genome-scale metabolic networks and prioritization of the identified targets through in silico analysis (WP4). In vitro experiments and ex vivo screening of metabolism-targeting agents will functionally validate metabolic vulnerabilities and their associated response biomarkers. We will also train a model to inform clinicians about the effectiveness of innovative therapeutic options (WP5) and patients’ perspectives (WP6), that will guide future clinical practice.
Network	ERA PerMed
Call	2nd Joint Transnational Call for Proposals (2019)

Project partner

Number	Name	Role	Country
1	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) srl, IRCCS	Coordinator	Italy
2	Charité University Medicine Berlin	Partner	Germany
3	University of Helsinki	Partner	Finland
4	Inserm Délégation Régionale Nord Ouest	Partner	France
5	University of Navarra	Partner	Spain
6	Uppsala University	Partner	Sweden