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Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts 02115

Stromal cell-derived factor (SDF)-1 mediates migration of normal hematopoietic stem cells, but its role in hematological malignancies is undefined. In this study, we detected SDF-1 in bone marrow (BM) plasma from 10 patients with MM (multiple myeloma; 2.6 ± 1.5 ng/ml) and BM stromal cell culture supernatants from 5 patients with MM (0.6 ± 0.2 ng/ml). We show that SDF-1 promotes proliferation, induces migration, and protects against dexamethasone-induced apoptosis in MM cells, but these effects are only modest. In MM cell lines and patient MM cells, SDF-1 induces phosphorylation of p42/44 mitogen-activated protein kinase, as well as Akt and its downstream target Bad, and also activates nuclear factor-B. In the BM milieu, SDF-1 up-regulates secretion of interleukin 6 and vascular endothelial growth factor in BM stromal cells, which promote tumor cell growth, survival, and migration. These data demonstrate that SDF-1 promotes growth, migration and drug resistance of MM cells in the BM microenvironment, but these effects are only modest, SDF-1 therefore does not represent a target for novel therapeutics in this disease.

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