Expression of the bcl-2 family of pro- and anti-apoptotic genes in multiple myeloma and normal plasma cells: regulation during interleukin-6(IL-6)-induced growth and survival

Eur J Haematol. 2002 Aug;69(2):76-89. doi: 10.1034/j.1600-0609.2002.01549.x.


Aberrant expression of genes regulating apoptosis/survival seems to be essential in the stepwise development of human multiple myeloma (MM). In this paper we have compared the expression of bcl-2 family pro- and anti-apoptotic genes in MM cell lines, primary MM cells and normal plasma cells. The Bcl-2, Mcl-1, Bcl-xL/S, Bcl-w, Bax, Bak, and Bad were shown to be expressed in both malignant and non-neoplastic, normal plasma cells. Quantitative analysis revealed that the malignant phenotype seemed to correlate with an elevated expression of Mcl-1, a decreased expression of Bax and, to a lesser extent, an increased Bcl-2/Bax expression ratio. The possible influence of interleukin-6 (IL-6) in regulating the expression of the bcl-2-related genes was also examined. Using the IL-6-dependent MM cell lines U-1958 and U-266-1970 it was clearly shown that IL-6 deprivation induced cell cycle arrest in both cell lines, whereas apoptosis was only detected in the U-1958 cells. Furthermore, the anti-apoptotic proteins Bcl-2, Mcl-1 and Bcl-xL were down-regulated, while the expression of the pro-apoptotic Bax protein was increased. To conclude, we suggest that the expression pattern of the Bcl-2 family of proteins separates the malignant phenotype of MM from normal plasma cells, and that the protecting effect of IL-6 may be conducted via an altered balance between these proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Division / drug effects
  • Cell Division / genetics
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Genes, bcl-2 / drug effects*
  • Humans
  • Interleukin-6 / pharmacology*
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / pathology
  • Plasma Cells / drug effects
  • Plasma Cells / pathology
  • Plasma Cells / physiology*
  • Tumor Cells, Cultured


  • Interleukin-6