Ricerc@Sapienza

Acute Myeloid Leukemia (AML) is a highly heterogenous disease characterized by a poor prognosis, with several sub-entities defined by a different genomic background that results in different responses to therapies and risk of relapse from resistant founding clone and/or for a rapid clonal evolution. Among AML patients, the subgroup with complex karyotype (CK) shows a dismal prognosis, thus representing a major unmet clinical need, requiring novel approaches possibly by tailored intervention. In the attempt to find additional druggable targets able to improve the current therapeutic arsenal, targeting AML cell metabolism is an emerging novel strategy. However, thus far, published studies report the impact of metabolism on AML samples without taking into account their genomic background. Indeed, the metabolic profile of AML with CK appears to be unexplored. This project aims to explore the potential benefit of metabolism-targeted therapy in CK-AML patients. For this purpose, we plan i) to analyze the Signal Transduction Pathways activation and the resulting metabolic profile of AML; ii) to study the proteomic and the resulting metabolic profile of CK-AML cell lines and primary samples performing different culture conditions in order to understand how their metabolism, signaling, cell growth and survival are influenced by the availability of carbon sources; iii) to evaluate the activity of molecules targeting metabolism and related signaling. With this project, we expect to expand the biological knowledge of CK-AML and translate this knowhow in the screening of new molecularly targeted agents attempting to achieve an amelioration of CK-AML clinical prognosis.