Targeting XIAP Via Degradation of MDM-2 By MX69 in Aggressive Lymphomas

Conclusion: Our data suggests that in vitro exposure of a wide variety of B-cell lymphoma cell lines (including BL, DLBCL, MCL or RRCL) to MX69 resulted in anti-tumor activity. Perhaps related to its anti-tumor effects, MX69 inhibited XIAP levels. These findings are similar to prior SiRNA XIAP knockdown experiments. Strong synergistic activity was observed when XIAP was combined with various chemotherapy agents and small molecules inhibitors (such as Venetoclax, ixazomib or ibrutinib). Ex vivo experiments using primary tumor cells isolated from lymphoma patients and lymphoma mouse models are been planned. Targeting Mdm2 and XIAP can be an attractive therapeutic strategy in patients with Rituximab-sensitive or -resistant B-cell lymphoma.DisclosuresNo relevant conflicts of interest to declare.

Source: Blood - November 21, 2018 Category: Hematology Authors: Khan, S., Runckel, K., Mavis, C., Barth, M. J., Hernandez-Ilizaliturri, F. J. Tags: 625. Lymphoma: Pre-Clinical-Chemotherapy and Biologic Agents Source Type: research