Defining genomic events involved in the evolutionary trajectories of myeloma and its precursor conditions

Monika Chojnacka, Benjamin Diamond, Ola Landgren, Francesco Maura

Research output: Contribution to journalArticlepeer-review

Abstract

All multiple myeloma (MM) patients have a preceding, asymptomatic expansion of clonal plasma cells, clinically recognized as monoclonal gammopathy of undetermined significance or smoldering multiple myeloma (SMM). While the majority of patients with monoclonal gammopathy of undetermined significance have a very small rate of progression, SMM is a widely heterogeneous condition where a fraction of patients will progress to symptomatic MM rather quickly, while others will experience an indolent clinical course. The differentiation between progressive and stable precursor condition thus represents one of the most important unmet clinical needs in the MM community. The ability to identify high-risk patients before major clonal expansion and onset of end-organ damage would enable strategies for early prevention and perhaps more effective intervention. All proposed criteria to predict the progression of myeloma precursor condition are built around indirect markers of disease burden and, therefore, are generally able to accurately identify only a small fraction of patients in whom progression to MM is already occurring. Leveraging whole genome and exome sequencing, it has been shown that patients with stable myeloma precursor conditions are characterized by either absence or lower prevalence of distinct genomic events that are detectable in progressive precursor condition years before the progression. In this review, we discuss evolving genomic concepts and tools; and their ability to differentiate myeloma precursor conditions into two distinct entities: one benign (monoclonal gammopathy of benign significance) and another malignant (asymptomatic multiple myeloma).

Original languageEnglish (US)
JournalSeminars in Oncology
DOIs
StateAccepted/In press - 2022
Externally publishedYes

Keywords

  • Chromothripsis
  • Copy- number variation
  • Multiple myeloma
  • Mutational signature

ASJC Scopus subject areas

  • Hematology
  • Oncology

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