Natural killer (NK) cells are key innate immune effectors against multiple myeloma, their activity declining in multiple myeloma patients with disease progression. To identify the mechanisms underlying NK cell functional impairment, we characterized the distribution of functionally distinct NK cell subsets in the bone marrow of multiple myeloma-bearing mice. Herein we report that the number of ...

Despite recent advances in targeted treatments for multiple myeloma, optimal molecular therapeutic targets have yet to be identified. To functionally identify critical molecular targets, we conducted a genome-scale lethality study in multiple myeloma cells using siRNAs. We validated the top 160 lethal hits with four siRNAs per gene in three multiple myeloma cell lines and two non-myeloma cell l...

Multiple myeloma is characterized by the malignant growth of immunoglobulin producing plasma cells, predominantly in the bone marrow. The effects of primary human mesenchymal stromal cells on the differentiation phenotype of multiple myeloma cells were studied by co-culture experiments. The incubation of multiple myeloma cells with bone marrow-derived mesenchymal stromal cells resulted in signi...

PURPOSE The alkylating agent melphalan prolongs survival in patients with multiple myeloma; however, it is associated with toxicities and development of drug-resistance. Here, we evaluated the efficacy of melphalan-flufenamide (mel-flufen), a novel dipeptide prodrug of melphalan in multiple myeloma. EXPERIMENTAL DESIGN Multiple myeloma cell lines, primary patient cells, and the human multiple...

PURPOSE The onset of drug resistance is a major cause of treatment failure in multiple myeloma. Although increasing evidence is defining the role of miRNAs in mediating drug resistance, their potential activity as drug-sensitizing agents has not yet been investigated in multiple myeloma. EXPERIMENTAL DESIGN Here we studied the potential utility of miR-221/222 inhibition in sensitizing refract...

PURPOSE The aim of this study was to investigate the angiogenic role of the hepatocyte growth factor (HGF)/cMET pathway and its inhibition in bone marrow endothelial cells (EC) from patients with multiple myeloma versus from patients with monoclonal gammopathy of undetermined significance (MGUS) or benign anemia (control group). EXPERIMENTAL DESIGN The HGF/cMET pathway was evaluated in ECs fr...

Insulin-like growth factor-1 (IGF-1), insulin, and IL-6 are dysregulated in multiple myeloma pathogenesis and may also contribute to multiple myeloma etiology. To examine their etiologic role, we prospectively analyzed concentrations of serologic markers in 493 multiple myeloma cases and 978 controls from 8 cohorts in the Multiple Myeloma Cohort Consortium. We computed odds ratios (ORs) and 95%...

we report a case of multiple myeloma that presented with anorexia, fatigue, high erythrocyte sedimentation rate, bone marrow plasmacytosis of more than 30%, polyuria,and low urine specific gravity. this unusual presentation was diagnosed as nephrogenic diabetes insipidus secondary to a proximal tubular dysfunction. the tubular functional disturbance appeared to be related to the presence of lam...

Autoimmune autonomic ganglionopathy is an autonomic disorder that occurs as a symptom of paraneoplastic neurological syndrome. To date, there have been no reports on multiple myeloma with autoimmune autonomic ganglionopathy. A 37-year-old Japanese woman suffered from orthostatic hypotension was diagnosed with multiple myeloma (IgG kappa type), and a serological examination revealed the presence...

Multiple myeloma - a neoplastic proliferation of plasma cell is the second most common blood cancer. Multiple myeloma is characterized by neoplastic proliferation of the plasma cells. These cells infiltrate variety of organs. Infiltration by immature neoplastic cells and overproduction of monoclonal immunoglobulin chain is responsible for clinical manifestations of multiple myeloma. The most co...