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BMP-4 and BMP-6 are overexpressed in the multiple myeloma bone marrow samples

Multiple myeloma (MM) is a B-lymphocyte neoplasia characterized by the slow proliferation of plasma-cells in bone marrow (BM) and bone destruction. In vitro, several BMPs have the ability to inhibit proliferation and elicit apoptosis of myeloma cells. We examined the expression of BMPs and their receptors in MM BM samples and tested the effect of BMP-2 and BMP-6 on myeloma cells in vitro. BM was obtained from MM patients (n = 25) and control subjects (n = 6) after the informed consent. cDNA was extracted from mononuclear BM cells and amplified by quantitative PCR, using TaqMan assays (Applied Biosystems) for BMP-2, BMP-4 and BMP-6, and Alk-2, Alk-3, Alk-6 and RII receptors, and expressed as the relative amounts of RNA (mean ± SD) for target genes normalized to GPDH, using the standard curve method. Primary MM samples and human myeloma line NCI H-929 were cultured for 48 hours and treated by BMP-2 or BMP-6 (500 ng/mL for both). BMP-2, BMP-4 and BMP-6 expression was significantly higher in MM BM samples compared with control BM, with significant positive correlation of BMP-6 expression and plasma-cell percentage in MM samples. Upon in vitro BMP-2 or BMP-6 treatment, moderate increase in the death/apoptotic cell number and expression of pro-apoptotic molecules were observed. We found that BMPs are over-expressed in MM BM samples, indicating their role in BM compensatory mechanism to induce malignant MM cell death and apoptosis. Further studies are needed to explore possible clinical application of BMPs in MM treatment.