Publication

Cell of Origin and Genetic Alterations in the Pathogenesis of Multiple Myeloma

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Last modified
  • 05/15/2025
Type of Material
Authors
    Benjamin G. Barwick, Emory UniversityVikas Gupta, Emory UniversityPaula M Vertino, Emory UniversityLawrence Boise, Emory University
Language
  • English
Date
  • 2019-05-21
Publisher
  • Frontiers Media
Publication Version
Copyright Statement
  • © 2019 Barwick, Gupta, Vertino and Boise.
License
Final Published Version (URL)
Title of Journal or Parent Work
ISSN
  • 1664-3224
Volume
  • 10
Issue
  • MAY
Start Page
  • 1121
End Page
  • 1121
Grant/Funding Information
  • BB is supported by Postdoctoral Fellowship PF-17-109-1-TBG from the American Cancer Society.
  • This study was supported in part by Winship Cancer Institute of Emory University and NIH/NCI award number P30CA138292.
  • LB is supported by NIH/NCI R01 CA192844 and an Answer Fund award from the MMRF.
Abstract
  • B cell activation and differentiation yields plasma cells with high affinity antibodies to a given antigen in a time-frame that allows for host protection. Although the end product is most commonly humoral immunity, the rapid proliferation and somatic mutation of the B cell receptor also results in oncogenic mutations that cause B cell malignancies including plasma cell neoplasms such as multiple myeloma. Myeloma is the second most common hematological malignancy and results in over 100,000 deaths per year worldwide. The genetic alterations that occur in the germinal center, however, are not sufficient to cause myeloma, but rather impart cell proliferation potential on plasma cells, which are normally non-dividing. This pre-malignant state, referred to as monoclonal gammopathy of undetermined significance or MGUS, provides the opportunity for further genetic and epigenetic alterations eventually resulting in a progressive disease that becomes symptomatic. In this review, we will provide a brief history of clonal gammopathies and detail how some of the key discoveries were interwoven with the study of plasma cells. We will also review the genetic and epigenetic alterations discovered over the past 25 years, how these are instrumental to myeloma pathogenesis, and what these events teach us about myeloma and plasma cell biology. These data will be placed in the context of normal B cell development and differentiation and we will discuss how understanding the biology of plasma cells can lead to more effective therapies targeting multiple myeloma.
Author Notes
Keywords
Research Categories
  • Health Sciences, Immunology
  • Biology, Genetics
  • Biology, Cell

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