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A systematic literature review on clonal evolution events preceding relapse in multiple myeloma

Maja Zimmer Jakobsen1, Rasmus Froberg Brøndum2, Henrik Gregersen1

  • 1Department of Hematology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.

Critical Reviews in Oncology/Hematology
|November 16, 2024
PubMed

Insights

Multiple myeloma (MM) remains incurable due to drug resistance. This review identifies genetic and non-genetic factors driving clonal evolution in relapsed MM, highlighting the need for high-resolution methods to understand tumor heterogeneity.

Area of Science:

  • Hematology
  • Cancer Genomics
  • Evolutionary Biology

Background:

  • Multiple myeloma (MM) is an incurable hematological malignancy.
  • Treatment resistance is a major challenge in managing MM, leading to disease relapse.
  • Understanding the mechanisms of clonal evolution is crucial for overcoming resistance.

Purpose of the Study:

  • To systematically review and identify determinants of clonal evolution driving relapse and drug resistance in MM.
  • To characterize genetic and non-genetic factors contributing to tumor heterogeneity in relapsed MM.
  • To suggest optimal methods for assessing clonal evolution in MM.

Main Methods:

  • Systematic literature search of publications on clonal evolution in relapsed MM.
  • Screening of 631 non-duplicate publications, with 28 articles included for data extraction.
  • Analysis of genetic alterations, mutational signatures, evolutionary trajectories, and non-genetic determinants.

Main Results:

  • Key topics identified include genetic alterations, mutational signatures, evolutionary trajectories, and non-genetic determinants.
  • Factors like MAPK-Ras mutations and chromosomal changes (bands 1 and 17) drive clonal diversification and increase tumor mutation burden.
  • APOBEC activity and melphalan treatment significantly impact MM genome clonal composition.

Conclusions:

  • Clonal evolution significantly contributes to relapse and drug resistance in multiple myeloma.
  • Understanding tumor heterogeneity requires comprehensive analysis of genetic and non-genetic factors.
  • Combining high-resolution methods is recommended for accurate assessment of clonal evolution in MM.
Keywords:
Clonal evolutionDrug resistanceGenetic alterationsMultiple myelomaMutational Signatures

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