Multiple myeloma cells expressing low levels of CD138 have an immature phenotype and reduced sensitivity to lenalidomide

Int J Oncol. 2012 Sep;41(3):876-84. doi: 10.3892/ijo.2012.1545. Epub 2012 Jul 4.


CD138 expression is a hallmark of plasma cells and multiple myeloma cells. However, decreased expression of CD138 is frequently observed in plasma cells of myeloma patients, although the clinical significance of this is unclear. To evaluate the significance of low expression of CD138 in MM, we examined the phenotypes of MM cells expressing low levels of CD138. Flow cytometric analysis of primary MM cells revealed a significant decrease in CD138 expression in patients with relapsed/progressive disease compared with untreated MM patients. Patients with low levels of CD138 had a worse overall survival compared with patients with high levels of CD138, in newly diagnosed patients and patients receiving high-dose chemotherapy followed by autologous stem-cell transplantation. Two MM cell lines, KYMM-1 (CD138- low) and KYMM-2 (CD138- high), were established from a single MM patient with decreased CD138 expression. High expression of BCL6 and PAX5, and downregulation of IRF4, PRDM1 and XBP1 was observed in KYMM-1 compared with KYMM-2 cells, indicative of the immature phenotype of KYMM-1. KYMM-1 was less sensitive to lenalidomide than KYMM-2, while no difference in sensitivity to bortezomib was observed. KYMM-2 cells were further divided in CD138+ and CD138- fractions using anti-CD138-coated magnetic beads. CD138- cells sorted from the KYMM-2 cell line also showed high BCL6, low IRF4 expression and decreased sensitivity to lenalidomide compared with CD138+ cells. Our observations suggest that low CD138 expression relates to i) poor prognosis, ii) immature phenotype and iii) low sensitivity to lenalidomide. The observed distinct characteristics of CD138 low MM cells, suggest this should be recognized as a new clinical entity. Establishment of a treatment strategy for MM cells expressing low levels of CD138 is needed to improve their poor outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Apoptosis
  • Biomarkers, Tumor
  • Boronic Acids / pharmacology
  • Bortezomib
  • Cell Line, Tumor
  • DNA Methylation
  • DNA-Binding Proteins / metabolism
  • Drug Resistance, Neoplasm
  • Female
  • Flow Cytometry
  • Humans
  • Interferon Regulatory Factors / metabolism
  • Lenalidomide
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / metabolism*
  • PAX5 Transcription Factor / metabolism
  • Phenotype
  • Positive Regulatory Domain I-Binding Factor 1
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-6
  • Pyrazines / pharmacology
  • Regulatory Factor X Transcription Factors
  • Repressor Proteins / metabolism
  • Syndecan-1 / metabolism*
  • Thalidomide / analogs & derivatives*
  • Thalidomide / pharmacology
  • Transcription Factors / metabolism
  • X-Box Binding Protein 1


  • BCL6 protein, human
  • Biomarkers, Tumor
  • Boronic Acids
  • DNA-Binding Proteins
  • Interferon Regulatory Factors
  • PAX5 Transcription Factor
  • PAX5 protein, human
  • Proto-Oncogene Proteins c-bcl-6
  • Pyrazines
  • Regulatory Factor X Transcription Factors
  • Repressor Proteins
  • Syndecan-1
  • Transcription Factors
  • X-Box Binding Protein 1
  • XBP1 protein, human
  • interferon regulatory factor-4
  • PRDM1 protein, human
  • Thalidomide
  • Bortezomib
  • Positive Regulatory Domain I-Binding Factor 1
  • Lenalidomide