fk-866 has been researched along with Waldenstrom-Macroglobulinemia* in 1 studies
1 other study(ies) available for fk-866 and Waldenstrom-Macroglobulinemia
Article | Year |
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Dual NAMPT and BTK Targeting Leads to Synergistic Killing of Waldenström Macroglobulinemia Cells Regardless of MYD88 and CXCR4 Somatic Mutation Status.
Nicotinamide phosphoribosyltransferase (Nampt) regulates intracellular NAD. 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 macroglobulinemia cells exhibit high levels of Nampt compared with normal B cells. Loss of function studies suggested a potential oncogenic role of Nampt in Waldenström macroglobulinemia cells, and BTK-inhibitor ibrutinib and FK866 resulted in a significant and synergistic anti-Waldenström macroglobulinemia cell death, regardless of MYD88 and CXCR4 mutational status. Cell death was associated with: (i) activation of caspase-3, PARP and downregulation of Mcl-1, (ii) enhanced intracellular ATP and NAD. Our results show intracellular NAD Topics: Acrylamides; Adenine; Agammaglobulinaemia Tyrosine Kinase; Animals; B-Lymphocytes; Caspase 3; Cell Death; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cytokines; Humans; Mice; Mice, SCID; Mutation; Myeloid Cell Leukemia Sequence 1 Protein; Myeloid Differentiation Factor 88; NF-kappa B; Nicotinamide Phosphoribosyltransferase; Piperidines; Poly(ADP-ribose) Polymerases; Protein-Tyrosine Kinases; Pyrazoles; Pyrimidines; Receptors, CXCR4; Signal Transduction; Waldenstrom Macroglobulinemia | 2016 |