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Prepublished online as a Blood First Edition Paper on September 5, 2002; DOI 10.1182/blood-2002-06-1874.

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Blood, 15 January 2003, Vol. 101, No. 2, pp. 703-705

NEOPLASIA
Brief report

Targeting p38 MAPK inhibits multiple myeloma cell growth in the bone marrow milieu

Teru Hideshima, Masaharu Akiyama, Toshiaki Hayashi, Paul Richardson, Robert Schlossman, Dharminder Chauhan, and Kenneth C. Anderson

From the Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, MA.

p38 mitogen-activated protein kinase (MAPK) is a member of the MAPK family which is activated by cytokines and growth factors, but its role in pathogenesis of multiple myeloma (MM) is unknown. In this study, we demonstrate that the specific p38 MAPK inhibitor VX-745 inhibits interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) secretion in bone marrow stromal cells (BMSCs), without affecting their viability. Tumor necrosis factor alpha (TNF-alpha )-induced IL-6 secretion in BMSCs is also inhibited by VX-745. Importantly, VX-745 inhibits both MM cell proliferation and IL-6 secretion in BMSCs triggered by adherence of MM cells to BMSCs, suggesting that it can inhibit paracrine MM cell growth in the BM milieu and overcome cell adhesion-related drug resistance. These studies therefore identify p38 MAPK as a novel therapeutic target to overcome drug resistance and improve patient outcome in MM.

© 2003 by The American Society of Hematology.
 

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