The broad objective of the project is to study the role of two protein partners of AF4 and MLL-AF4, i.e. 14-3-3 theta and fibroblast growth factor receptor 2 (FGFR2), in the molecular pathogenesis of t(4;11) acute lymphoblastic leukemia (ALL). Specific aims of the project are to: 1. evaluate the effects of 14-3-3 theta on AF4 and MLL-AF4 function; 2. analyze the role of FGFR2 on MLL-AF4 transactivity; 3. test 14-3-3 theta and FGFR2 as therapeutic targets. The t(4;11)(q21;q23) translocation, a frequent cause of ALL, creates a fusion gene, which encodes the MLL-AF4 oncoprotein. The t(4;11) leukemia has very poor prognosis and no therapy. Identification of AF4 and MLL-AF4 molecular partners may give useful information to design targeted therapies. Our preliminary data indicate 14-3-3 theta and FGFR2 are direct interactors of AF4 and MLL-AF4, respectively. Specific drugs exist that may target 14-3-3 theta and FGFR2. Hopefully, our study points the way for molecular therapy of t(4;11) ALL.
From protein-protein interaction studies new potential therapeutic targets to treat the MLL-related acute lymphoblastic leukemias / Esposito, Gabriella. - (2012). (Intervento presentato al convegno From protein-protein interaction studies new potential therapeutic targets to treat the MLL-related acute lymphoblastic leukemias nel 03/11/2014).
From protein-protein interaction studies new potential therapeutic targets to treat the MLL-related acute lymphoblastic leukemias
ESPOSITO, GABRIELLA
2012
Abstract
The broad objective of the project is to study the role of two protein partners of AF4 and MLL-AF4, i.e. 14-3-3 theta and fibroblast growth factor receptor 2 (FGFR2), in the molecular pathogenesis of t(4;11) acute lymphoblastic leukemia (ALL). Specific aims of the project are to: 1. evaluate the effects of 14-3-3 theta on AF4 and MLL-AF4 function; 2. analyze the role of FGFR2 on MLL-AF4 transactivity; 3. test 14-3-3 theta and FGFR2 as therapeutic targets. The t(4;11)(q21;q23) translocation, a frequent cause of ALL, creates a fusion gene, which encodes the MLL-AF4 oncoprotein. The t(4;11) leukemia has very poor prognosis and no therapy. Identification of AF4 and MLL-AF4 molecular partners may give useful information to design targeted therapies. Our preliminary data indicate 14-3-3 theta and FGFR2 are direct interactors of AF4 and MLL-AF4, respectively. Specific drugs exist that may target 14-3-3 theta and FGFR2. Hopefully, our study points the way for molecular therapy of t(4;11) ALL.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
