Bortezomib inhibits the survival and proliferation of bone marrow stromal cells

BACKGROUND: Bortezomib is widely used for the treatment of multiple myeloma. Bone marrow stromal cells (BMSCs) endow myeloma cells with survival and growth advantages. However, the influence of bortezomib on BMSCs is not well elucidated. We examined the effects of bortezomib on the survival and growth of BMSCs in vitro. METHODS: The effects of bortezomib on the survival and proliferation of the BMSC MS-5 cell line and on BMSCs obtained from healthy individuals (N=4) and newly diagnosed myeloma patients (N=5) were investigated in vitro. Transmembrane cell migration was evaluated using the Transwell system. A short interfering RNA strategy was used to knock down the expression of chemokine (CXC motif) ligand 12 (CXCL12) mRNA. To examine the effects of bortezomib-exposed BMSCs on the migration and localization of myeloma cells, MS-5 monolayers were treated with bortezomib for 24 hr, washed, and then overlaid with human RPMI8226 myeloma cells. RESULTS: Bortezomib inhibited BMSC proliferation in a concentration-dependent manner, and induced cellular apoptosis. Bortezomib decreased CXCL12 production by BMSCs. Knockdown of CXCL12 mRNA in BMSCs revealed that CXCL12 served as an autocrine growth factor. Short-term bortezomib treatment of BMSC monolayers reduced the tendency of myeloma cells to locate to positions under the monolayers. CONCLUSION: Bortezomib inhibits the survival and growth of BMSCs via downregulation of CXCL12, which may contribute to the clinical effects of this agent.

Diagnostic and Prognostic Implications of Spine Magnetic Resonance Imaging at Diagnosis in Patients with Multiple Myeloma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The aim of this study is to determine the diagnostic and prognostic role of baseline spinal magnetic resonance imaging (MRI) in patients with multiple myeloma. MATERIALS AND METHODS: We enrolled patients newly diagnosed with multiple myeloma from 2004-2011 at a single center. Abnormal MRI findings that were not detected in radiographs have been analyzed and categorized as malignant compression fractures or extramedullary plasmacytoma. The bone marrow (BM) infiltration patterns on MRI have been classified into five categories. RESULTS: A total of 113 patients with a median age of 65 years (range, 40 to 89 years) were enrolled in the study. Malignant compression fractures not detected in the bone survey were found in 26 patients (23.0%), including three patients (2.6%) with no related symptoms or signs. Extramedullary plasmacytoma was detected in 22 patients (19.5%), including 15 (13.3%) with epidural extension of the tumor. Of these 22 patients, 11 (50.0%) had no relevant symptoms or signs. The presence of malignant compression fractures did not influence overall survival; whereas non-epidural extramedullary plasmacytoma was associated with poor overall survival in the multivariate analysis (hazard ratio, 3.205; 95% confidence interval [CI], 1.430 to 9.845; p=0.042). During the follow-up for a median of 21 months (range, 1 to 91 months), overall survival with the mixed BM infiltrative pattern (median, 24.0 months; 95% CI, 22.9 to 25.1 months) was shorter than those with other patterns (median 56 months; 95% CI, 48.9 to 63.1 months; p=0.030). CONCLUSION: These results indicate that spine MRI at the time of diagnosis is useful for detecting skeletal lesions and predicting the prognosis in patients with multiple myeloma.