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 (Mvarphis), a type of stromal cells, on myeloma cell survival and response to chemotherapy. We showed that Mvarphi, in particular tumor-associated Mvarphi, is a protector of mye...

The objective of this study was to determine the effects of an luteinizing hormone-releasing hormone (LHRH)-I antagonist, Cetrorelix, on humanmultiple myeloma (MM) cells and to elucidate the mechanisms of action. We showed that LHRH-I and LHRHR-I genes were expressed in MM cell lines and primary MM cells. Treatment with Cetrorelix inhibited growth and colony-forming ability of myeloma cells, in...

Idiotype (Id) protein, secreted by myeloma cells, is a tumor-specific antigen. Id-based immunotherapy has been explored in patients with myeloma, and results were disappointing. Although previous studies have shown that Id-specific CTLs are able to lyse myeloma cells, it is unclear whether other types of Id-specific T cells, such as type-1 T-helper (Th1) and type-2 T-helper (Th2) cells, are als...

To describe the prevalence of comorbidity and its impact on survival in newly diagnosed multiple myeloma patients compared with population controls. Cases of newly diagnosed symptomatic multiple myeloma during the 2005-2012 period were identified in the Danish National Multiple Myeloma Registry. For each myeloma patient, 10 members of the general population matched by age and sex were chosen fr...

Bone destruction is very common in myeloma and occurs in over 80% of patients. It is responsible for some of the most devastating complications of the disease including pathologic fractures, bone pain and hypercalcemia. However, the mechanisms responsible for bone destruction in myeloma and the inability of the osteoblast to repair bone lesions even when the disease is in clinical remission rem...

Osteoblast impairment occurs within multiple myeloma cell infiltration into the bone marrow. Canonical Wnt signaling activation in osteoprogenitor cells is involved in osteoblast formation through the stabilization of dephosphorylated beta-catenin and its nuclear translocation. The effects of multiple myeloma cells on Wnt signaling in human mesenchymal/osteoprogenitor cells are unclear. In 60 m...

Multiple myeloma develops primarily inside the bone marrow microenvironment, that confers pro-survival signals and drug resistance. 3D cultures that reproduce multiple myeloma-bone marrow interactions are needed to fully investigate multiple myeloma pathogenesis and response to drugs. To this purpose, we exploited the 3D Rotary Cell Culture System bioreactor technology for myeloma-bone marrow c...

Myeloma bone disease is due to interactions of myeloma cells with the bone marrow microenvironment, and is associated with pathologic fractures, neurologic symptoms and hypercalcemia. Adjacent to myeloma cells, the formation and activation of osteoclasts is increased, which results in enhanced bone resorption. The recent characterization of the essential cytokine of osteoclast cell biology, rec...

The objective of this study was to determine the effects of an luteinizing hormone-releasing hormone (LHRH)-I antagonist, Cetrorelix, on human multiple myeloma (MM) cells and to elucidate the mechanisms of action. We showed that LHRH-I and LHRHR-I genes were expressed in MM cell lines and primary MM cells. Treatment with Cetrorelix inhibited growth and colony-forming ability of myeloma cells, i...

Ibrutinib (Imbruvica), a small-drug inhibitor of Bruton tyrosine kinase (BTK), is currently undergoing clinical testing in patients with multiple myeloma, yet important questions on the role of BTK in myeloma biology and treatment are outstanding. Using flow-sorted side population cells from human myeloma cell lines and multiple myeloma primary samples as surrogate for the elusive multiple myel...