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 Citations (Scopus)

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

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Monocytes
Phosphotransferases
Macrophages
Growth
Neoplasms
Residual Neoplasm
Mitogens
Mitosis
Cell Communication
Pharmacology
Apoptosis
Therapeutics

Keywords

  • Bone marrow pathology
  • Macrophages
  • Myeloma

ASJC Scopus subject areas

  • Hematology

Cite this

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

In: British Journal of Haematology, Vol. 160, No. 6, 01.03.2013, p. 779-784.

Research output: Contribution to journalArticle

Hebron, E, Hope, C, Kim, J, Jensen, JL, 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, vol. 160, no. 6, pp. 779-784. https://doi.org/10.1111/bjh.12175
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. / MAP3K8 kinase regulates myeloma growth by cell-autonomous and non-autonomous mechanisms involving myeloma-associated monocytes/macrophages. In: British Journal of Haematology. 2013 ; Vol. 160, No. 6. pp. 779-784.
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