Macrophages are an abundant component of myeloma microenvironment and protect myeloma cells from chemotherapy drug-induced apoptosis

Multiple myeloma remains an incurable disease. One of the major problems is that myeloma cells develop drug resistance on interaction with bone marrow stromal cells. In this study, we examined the effects of macrophages (M phi s), a type of stromal cells, on myeloma cell survival and response to chemotherapy. We showed that M phi, in particular tumor-associated M phi, is a protector of myeloma cells. The protective effect was dependent on direct contact between M phi s and myeloma cells. M phi s protected both myeloma cell lines and primary myeloma cells from spontaneous and chemotherapy drug-induced apoptosis by attenuating the activation and cleavage of caspase-dependent apoptotic signaling. These findings are clinically relevant because we found that CD68(+) M phi s heavily infiltrate the bone marrow of patients with myeloma but not the bone marrow of control patients. Thus, our results indicate that M phi s may contribute to myeloma cell survival and resistance to chemotherapeutic treatment in vivo. (Blood. 2009;114:3625-3628)