Myeloma stem cell concepts, heterogeneity and plasticity of multiple myeloma

Br J Haematol. 2013 Dec;163(5):551-64. doi: 10.1111/bjh.12563. Epub 2013 Sep 20.


Multiple myeloma (MM) is a haematological malignancy characterized by the accumulation of clonal plasma cells (PCs) in the bone marrow (BM). Although novel therapeutic strategies have prolonged survival of patients, the disease remains difficult to treat with a high risk of relapse. The failure of therapy is thought to be associated with a persistent population of the so-called MM stem cells or myeloma initiating cells (MIC) that exhibit tumour-initiating potential, self-renewal and resistance to chemotherapy. However, the population responsible for the origin and sustainability of tumour mass has not been clearly characterized so far. This review summarizes current myeloma stem cell concepts and suggests that high phenotypic and intra-clonal heterogeneity, together with plasticity potential of MM might be other contributing factors explaining discrepancies among particular concepts and contributing to the treatment failure.

Keywords: malignant plasma cells; multiple myeloma; myeloma stem cells; plasticity; precursor B cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antigens, Differentiation, B-Lymphocyte / analysis
  • Antigens, Neoplasm / analysis
  • B-Lymphocytes / pathology
  • Cell Dedifferentiation / genetics
  • Cell Hypoxia
  • Cell Lineage
  • Clone Cells / pathology
  • Gene Expression Regulation, Neoplastic
  • Gene Rearrangement, B-Lymphocyte
  • Humans
  • Immunoglobulin Class Switching
  • Models, Biological
  • Molecular Targeted Therapy
  • Multiple Myeloma / pathology*
  • Multiple Myeloma / therapy
  • Myeloma Proteins / analysis
  • Myeloma Proteins / genetics
  • Neoplastic Stem Cells / pathology*
  • PAX5 Transcription Factor / deficiency
  • PAX5 Transcription Factor / genetics
  • Plasma Cells / pathology


  • Antigens, Differentiation, B-Lymphocyte
  • Antigens, Neoplasm
  • Myeloma Proteins
  • PAX5 Transcription Factor
  • PAX5 protein, human