Plasma cells expression from smouldering myeloma to myeloma reveals the importance of the PRC2 complex, cell cycle progression, and the divergent evolutionary pathways within the different molecular subgroups

• Published in: Leukemia 2022-02, Vol.36 (2), p.591-595
• Main Authors: Boyle, Eileen M., Rosenthal, Adam, Ghamlouch, Hussein, Wang, Yan, Farmer, Phillip, Rutherford, Michael, Ashby, Cody, Bauer, Michael, Johnson, Sarah K., Wardell, Christopher P., Wang, Yubao, Hoering, Antje, Schinke, Carolina, Thanendrarajan, Sharmilan, Zangari, Maurizio, Barlogie, Bart, Dhodapkar, Madhav V., Davies, Faith E., Morgan, Gareth J., van Rhee, Frits, Walker, Brian A.
• Format: Article
• Language: English
• Subjects: 38; 38/39; 692/308/575; 692/499; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cancer Research; Cell Cycle; Critical Care Medicine; Disease Progression; Divergence; Evolution, Molecular; Gene expression; Gene Expression Profiling; Hematology; Humans; Intensive; Internal Medicine; Letter; Medicine; Medicine & Public Health; Multiple myeloma; Multiple Myeloma - genetics; Multiple Myeloma - metabolism; Multiple Myeloma - pathology; Oncology; Pathogenesis; Plasma cells; Plasma Cells - metabolism; Plasma Cells - pathology; Polycomb Repressive Complex 2 - genetics; Polycomb Repressive Complex 2 - metabolism; Prognosis; Signal Transduction; Smoldering; Smoldering Multiple Myeloma - genetics; Smoldering Multiple Myeloma - metabolism; Smoldering Multiple Myeloma - pathology; Subgroups
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/s41375-021-01379-y

Sequencing studies have shed some light on the pathogenesis of progression from smouldering multiple myeloma (SMM) and symptomatic multiple myeloma (MM). Given the scarcity of smouldering samples, little data are available to determine which translational programmes are dysregulated and whether the mechanisms of progression are uniform across the main molecular subgroups. In this work, we investigated 223 SMM and 1348 MM samples from the University of Arkansas for Medical Sciences (UAMS) for which we had gene expression profiling (GEP). Patients were analysed by TC-7 subgroup for gene expression changes between SMM and MM. Among the commonly dysregulated genes in each subgroup, PHF19 and EZH2 highlight the importance of the PRC2.1 complex. We show that subgroup specific differences exist even at the SMM stage of disease with different biological features driving progression within each TC molecular subgroup. These data suggest that MMSET SMM has already transformed, but that the other precursor diseases are distinct clinical entities from their symptomatic counterpart.