MAP3K8 kinase regulates myeloma growth by cell-autonomous and non-autonomous mechanisms involving myeloma-associated monocytes/macrophages

Ellen Hebron, Chelsea Hope, Jaehyup Kim, Jeffrey L. Jensen, Claire Flanagan, Neehar Bhatia, Ioanna Maroulakou, Constantine Mitsiades, Shigeki Miyamoto, Natalie Callander, Peiman Hematti, Fotis Asimakopoulos

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)779-784
Number of pages6
JournalBritish Journal of Haematology
Volume160
Issue number6
DOIs
StatePublished - Mar 1 2013
Externally publishedYes

Keywords

  • Bone marrow pathology
  • Macrophages
  • Myeloma

ASJC Scopus subject areas

  • Hematology

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    Hebron, E., Hope, C., Kim, J., Jensen, J. L., Flanagan, C., Bhatia, N., Maroulakou, I., Mitsiades, C., Miyamoto, S., Callander, N., Hematti, P., & Asimakopoulos, F. (2013). MAP3K8 kinase regulates myeloma growth by cell-autonomous and non-autonomous mechanisms involving myeloma-associated monocytes/macrophages. British Journal of Haematology, 160(6), 779-784. https://doi.org/10.1111/bjh.12175