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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- )-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.

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