Dual NAMPT and BTK Targeting Leads to Synergistic Killing of Waldenstrom Macroglobulinemia Cells Regardless of MYD88 and CXCR4 Somatic Mutation Status.

ABSTRACT:

Purpose

Nicotinamide phosphoribosyltransferase (Nampt) regulates intracellular NAD⁺ pool and is highly expressed in a number of malignancies. FK866, a selective inhibitor of Nampt, depletes intracellular NAD⁺ levels, thereby blocking cellular metabolism and triggering sensitization to other drugs and cell death. Here we characterized the antitumor effects of Nampt inhibition in Waldenström macroglobulinemia.

Experimental design

We investigated Nampt role in MW cells using both mRNA and protein expression analyses. We have also used loss-of-function approaches to investigate the growth and survival effects of Nampt on MW cells and further tested the anti-MW activity of dual Nampt and BTK inhibition in vitro and in vivo RESULTS: We found that Waldenström

SUBMITTER: Cea M 

PROVIDER: S-EPMC5771267 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature