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Updated: Jun 17, 2025

Establishment of a Human Multiple Myeloma Xenograft Model in the Chicken to Study Tumor Growth, Invasion and Angiogenesis
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Establishment of a Human Multiple Myeloma Xenograft Model in the Chicken to Study Tumor Growth, Invasion and Angiogenesis

Published on: May 1, 2015

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Deciphering the genetics and mechanisms of predisposition to multiple myeloma

Molly Went1, Laura Duran-Lozano2,3, Gisli H Halldorsson4

  • 1Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.

Nature Communications
|August 5, 2024
PubMed

Insights

Genetic predisposition to multiple myeloma (MM) involves longer telomeres and elevated B-cell maturation antigen (BCMA) and IL5RA levels. A specific variant in TNFRSF13B increases MM risk via amplified B-cell responses.

Area of Science:

  • Genetics
  • Oncology
  • Immunology

Background:

  • Multiple myeloma (MM) is an incurable plasma cell malignancy with a known heritable component.
  • The genetic mechanisms underlying MM predisposition are not fully understood.

Purpose of the Study:

  • To identify genetic loci associated with multiple myeloma (MM) risk.
  • To elucidate the causal mechanisms of inherited MM risk.

Main Methods:

  • Genome-wide association study (GWAS) of 10,906 MM cases and 366,221 controls.
  • Functional fine-mapping and Mendelian randomization analyses.

Main Results:

  • Identified 35 MM risk loci, including 12 novel loci.
  • Uncovered two causal mechanisms: longer telomeres and elevated plasma levels of B-cell maturation antigen (BCMA) and IL5RA.
  • The risk variant rs34562254-A at TNFRSF13B mediates increased BCMA and IL5RA, conferring a gain-of-function effect that amplifies B-cell responses and increases MM risk.

Conclusions:

  • Genetic predisposition to MM is linked to specific molecular pathways.
  • Understanding these genetic factors, such as TNFRSF13B variants, offers insights into MM pathogenesis and potential therapeutic targets.

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