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- Title
MAP3K8 kinase regulates myeloma growth by cell-autonomous and non-autonomous mechanisms involving myeloma-associated monocytes/macrophages.
- Authors
Hebron, Ellen; Hope, Chelsea; Kim, Jaehyup; Jensen, Jeffrey L; Flanagan, Claire; Bhatia, Neehar; Maroulakou, Ioanna; Mitsiades, Constantine; Miyamoto, Shigeki; Callander, Natalie; Hematti, Peiman; Asimakopoulos, Fotis
- Abstract
Benefit from cytotoxic therapy in myeloma may be limited by the persistence of residual tumour cells within protective niches. We have previously shown that monocytes/macrophages acquire a proinflammatory transcriptional profile in the myeloma microenvironment. Here we report constitutive activation of MAP3K8 kinase-dependent pathways that regulate the magnitude and extent of inflammatory activity of monocytes/macrophages within myeloma niches. In myeloma tumour cells, MAP3K8 acts as mitogen-induced MAP3K in mitosis and is required for TNFα-mediated ERK activation. Pharmacological MAP3K8 inhibition results in dose-dependent, tumour cell-autonomous apoptosis despite contact with primary stroma. MAP3K8 blockade may disrupt crucial macrophage-tumour cell interactions within myeloma niches.
- Publication
British journal of haematology, 2013, Vol 160, Issue 6, p779
- ISSN
1365-2141
- Publication type
Journal Article
- DOI
10.1111/bjh.12175