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Genetic Abnormalities in Extramedullary Multiple Myeloma.

Roisin McAvera1, John Quinn2,3, Philip Murphy2

  • 1Department of Pathology, Royal College of Surgeons in Ireland, D09 YD60 Dublin, Ireland.

International Journal of Molecular Sciences
|July 29, 2023
PubMed
Summary
This summary is machine-generated.

Extramedullary disease (EMD) in multiple myeloma (MM) is increasing and poorly understood. This review summarizes the genetic factors driving EMD, offering insights into this aggressive cancer's progression.

Keywords:
extramedullary myelomagenomicshigh-riskmultiple myeloma

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Area of Science:

  • Hematology
  • Oncology
  • Genetics

Background:

  • Extramedullary disease (EMD) is an aggressive manifestation of multiple myeloma (MM) where malignant plasma cells disseminate outside the bone marrow.
  • The incidence of EMD is rising with novel anti-myeloma therapies, presenting a significant clinical challenge.
  • Understanding the mechanisms of bone marrow escape and EMD development is crucial for improving patient outcomes.

Purpose of the Study:

  • To review and synthesize current knowledge on the genetic underpinnings of extramedullary disease in multiple myeloma.
  • To highlight key genetic alterations and epigenetic changes associated with EMD establishment and progression.

Main Methods:

  • Literature review focusing on genetic and epigenetic studies of extramedullary disease in multiple myeloma.
  • Synthesis of findings related to cytogenetic abnormalities, gene mutations, and epigenetic modifications in EMD.

Main Results:

  • High-risk cytogenetic abnormalities and specific gene signatures are linked to EMD.
  • Mutations in RAS signaling pathways are frequently observed in EMD.
  • Epigenetic alterations, particularly DNA hypermethylation in promoter regions, are increasingly recognized as drivers of EMD.

Conclusions:

  • The genetic landscape of EMD is distinct and involves specific molecular events enabling plasma cell dissemination.
  • Further research into the genomics and epigenomics of EMD is essential for developing targeted therapies.
  • Identifying EMD driver events can lead to better risk stratification and treatment strategies for multiple myeloma patients.