Bone morphogenetic proteins and receptors are over-expressed in bone-marrow cells of multiple myeloma patients and support myeloma cells by inducing ID genes

Leuk Res. 2010 Jun;34(6):742-51. doi: 10.1016/j.leukres.2009.10.016. Epub 2009 Nov 18.


We assessed the expression pattern and clinical relevance of BMPs and related molecules in multiple myeloma (MM). MM bone-marrow samples (n=32) had increased BMP4, BMP6, ACVR1 and ACVR2A, and decreased NOG expression compared with controls (n=15), with BMP6 having the highest sensitivity/specificity. Within MM bone-marrow, the source of BMPs was mainly CD138(+) plasma-cell population, and BMP6 and ACVR1 expression correlated with plasma-cell percentage. Using myeloma cell lines NCI H929 and Thiel we showed that BMPs induced ID1, ID2 and IL6, and suppressed CDKN1A and BAX gene expression, and BAX protein expression. Finally, BMPs partially protected myeloma cells from bortezomib- and TRAIL-induced apoptosis. We concluded that BMPs may be involved in MM pathophysiology and serve as myeloma cell biomarkers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Marrow Cells / metabolism*
  • Bone Marrow Cells / pathology
  • Bone Morphogenetic Protein Receptors / genetics*
  • Bone Morphogenetic Protein Receptors / metabolism
  • Bone Morphogenetic Proteins / genetics*
  • Bone Morphogenetic Proteins / metabolism
  • Case-Control Studies
  • Cell Proliferation
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Inhibitor of Differentiation Proteins / genetics*
  • Inhibitor of Differentiation Proteins / metabolism
  • Male
  • Middle Aged
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology
  • Tumor Cells, Cultured
  • Up-Regulation / genetics


  • Bone Morphogenetic Proteins
  • Inhibitor of Differentiation Proteins
  • Bone Morphogenetic Protein Receptors