Abstract
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.
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Acknowledgements
We thank all the patients and their families for their contributions to this study. BAW and GJM received grant support through a Translational Research Programme award from the Leukemia & Lymphoma Society (6602-20 and 6600-20).
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Designed the study: EMB, BAW, GJM, FVR. Analysed the data: EMB, AR, AH. Interpreted the data: EMB, BAW, FED, HG, YuW, GJM. Acquired the data: PF, MR, CA, MB, SKJ, CPW, YanW, CDS, ST, MZ, BB, MVD, FVR, GLM, FED. Wrote the manuscript: EMB, FED, BW. Reviewed the manuscript: all authors.
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Boyle, E.M., Rosenthal, A., Ghamlouch, H. et al. 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. Leukemia 36, 591–595 (2022). https://doi.org/10.1038/s41375-021-01379-y
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DOI: https://doi.org/10.1038/s41375-021-01379-y
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