Multiple Myeloma: Molecular Pathogenesis and Disease Evolution

Michael Heider, Katharina Nickel, Marion Högner, Florian Bassermann

Research output: Contribution to journalReview articlepeer-review

33 Scopus citations

Abstract

Background: Multiple myeloma is the second most common hematologic malignancy, which to date remains incurable despite advances in treatment strategies including the use of novel substances such as proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. Summary: The bone marrow-based disease is preceded by the 2 sequential premalignant conditions: monoclonal gammo-pathy of undetermined significance and smoldering myeloma. Plasma cell leukemia and extramedullary disease occur, when malignant clones lose their dependency on the bone marrow. Key genetic features of these plasma cell dyscrasias include chromosomal aberrations such as translocations and hyperdiploidy, which occur during error-prone physiologic processes in B-cell development. Next-generation sequencing studies have identified mutations in major oncogenic pathways and tumor suppressors, which contribute to the pathogenesis of multiple myeloma and have revealed insights into the clonal evolution of the disease, particularly along different lines of therapy. More recently, the importance of epigenetic alterations and the role of the bone marrow microenvironment, including immune and osteogenic cells, have become evident. Key Messages: We herein review the current knowledge of the pathogenesis of multiple myeloma, which is crucial for the development of novel targeted therapeutic strategies. These can contribute to the endeavor to make multiple myeloma a curable disease.

Original languageEnglish
Pages (from-to)672-681
Number of pages10
JournalOncology Research and Treatment
Volume44
Issue number12
DOIs
StatePublished - 1 Dec 2021

Keywords

  • Genetics
  • Multiple myeloma
  • Pathogenesis
  • Plasma cells

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