title: P53-MDM2 Pathway: Evidences for A New Targeted Therapeutic Approach in B-Acute Lymphoblastic Leukemia.
abstract: The tumor suppressor p53 is a canonical regulator of different biological functions, like apoptosis, cell cycle arrest, DNA repair, and genomic stability. This gene is frequently altered in human tumors generally by point mutations or deletions. Conversely, in acute lymphoblastic leukemia (ALL) genomic alterations ofTP53are rather uncommon, and prevalently occur in patients at relapse or with poor prognosis. On the other hand, p53 pathway is often compromised by the inactivation of its regulatory proteins, as MDM2 and ARF. MDM2 inhibitor molecules are able to antagonize p53-MDM2 interaction allowing p53 to exert tumor suppressor transcriptional regulation and to induce apoptotic pathways. Recent preclinical and clinical studies propose that MDM2 targeted therapy represents a promising anticancer strategy restoring p53 dependent mechanisms in ALL disease. Here, we discussed the use of new small molecule targeting p53 pathways as a promising drug target therapy in ALL.
authors.affiliation: Laboratory of Pre-Clinical and Translational Research, IRCCS - Referral Cancer Center of Basilicata Rionero in Vulture (PZ), Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Trino
authors.affiliation: Laboratory of Pre-Clinical and Translational Research, IRCCS - Referral Cancer Center of Basilicata Rionero in Vulture (PZ), Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: De Luca
authors.affiliation: Laboratory of Pre-Clinical and Translational Research, IRCCS - Referral Cancer Center of Basilicata Rionero in Vulture (PZ), Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Laurenzana
authors.affiliation: Laboratory of Pre-Clinical and Translational Research, IRCCS - Referral Cancer Center of Basilicata Rionero in Vulture (PZ), Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Caivano
authors.affiliation: CEINGE - Biotecnologie Avanzate S.C.a R.L.Naples, Italy; Department of Molecular Medicine and Medical Biotechnologies, Universita' degli Studi di Napoli Federico IINaples, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Del Vecchio
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology "L. and A. Seràgnoli," University of Bologna Bologna, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.affiliation: Scientific Direction, IRCCS - Referral Cancer Center of Basilicata Rionero in Vulture (PZ), Italy.
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Musto
keywords: MDM2; Nutlin-3a; acute lymphoblastic leukemia; p53; target therapy