THE BONE MARROW STROMAL ENVIRONMENT IS A MAJOR FACTOR IN MYELOMA CELL RESISTANCE TO DEXAMETHASONE

摘要: Dexamethasone (Dex), which is often used for the treatment of multiple myeloma, produces rapid reductions in tumor mass and improvement disease symptoms; however, it not curative, drug-resistant cells eventually emerge. To elucidate this apparent paradox, we tested effect bone marrow environment on myeloma cell response to drug. determine whether stroma provides sufficient amounts interleukin (IL)-6 protect against effects Dex, compared production IL-6 by stromal from four patients before, during, after exposure 10(-7) M found that even presence drug, continued produce IL-6, albeit reduced concentrations. We ability cells, purified seven sorting basis CD38 CD45 expression, two light-scatter parameters, Dex-induced apoptosis. In contrast mature CD38+CD45- were protected, coculture with very effectively protected immature CD38+CD45+ Dex. These data may explain palliative efficacy Dex provide a rationale combining antagonists overcome IL-6-mediated resistance cells.