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International Journal of Hematology

, Volume 78, Issue 2, pp 121–125 | Cite as

Recent Advances in Understanding the Pathogenesis of Anemia in Multiple Myeloma

  • Franco Silvestris
  • Marco Tucci
  • Cosima Quatraro
  • Franco Dammacco
Article

Abstract

Anemia is a prominent feature of multiple myeloma (MM) and is commonly associated with clinical progression of MM. In addition to being affected by a number of pathogenetic events, including imbalance of the cytokine network, inappropriate erythropoietin (EPO) levels, blood loss, and hemolysis, the erythroid matrix is chronically deteriorated by the malignant plasma cell clone that activates a cytotoxic mechanism directed at the erythroid progenitors. In particular, malignant plasma cells express very high levels of apoptogenic receptors, including both Fas ligand and tumor necrosis factor-related apoptosisinducing ligand, which trigger apoptosis of immature erythroblasts by stimulating specific death receptors, namely Fas and the complex DR4/DR5. Erythroid cells also weakly express the transcription factor GATA-1, which drives erythroblast maturation by inhibiting apoptosis through antiapoptotic molecules such as EPO and Bcl-xL. This newly discovered pathogenetic mechanism of anemia in MM is based on persistent erythroblast cytotoxicity within the bone marrow that leads to progressive destruction of the erythroid matrix.

Key words

Anemia Erythroblast apoptosis Fas-L Multiple myeloma TRAIL 

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Copyright information

© The Japanese Society of Hematology 2003

Authors and Affiliations

  • Franco Silvestris
    • 1
  • Marco Tucci
    • 1
  • Cosima Quatraro
    • 1
  • Franco Dammacco
    • 1
  1. 1.DIMO, Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical OncologyUniversity of BariBariItaly

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