Genotypic identification of polyclonal plasma cells in plasma cell dyscrasias shows an aberrant single-cell phenotype with clinical implications

Da Via, M. C.; Lazzaroni, F.; Matera, A.; Marella, A.; Maeda, A.; De Magistris, C.; Pettine, L.; Fabris, S.; Pioggia, S.; Marchetti, A.; Barbieri, M.; Lonati, S.; Cattaneo, A.; Tornese, M.; Scopetti, M.; Latifinavid, N.; Castellano, G.; Torricelli, F.; Neri, A.; Fokkema, C.; Cupedo, T.; Lionetti, M.; Passamonti, F.; Bolli, N.

doi:10.1101/2024.05.26.595470

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bioRxiv · 10.1101/2024.05.26.595470

Genotypic identification of polyclonal plasma cells in plasma cell dyscrasias shows an aberrant single-cell phenotype with clinical implications

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Abstract

Multiple Myeloma (MM) is driven by clonal plasma cell (PC)-intrinsic factors and changes in the tumorigenic microenvironment (TME). To investigate if residual polyclonal PCs (pPCs) are disrupted, single-cell (sc) RNAseq and sc B-cell receptor analysis were applied in a cohort of 46 samples with PC dyscrasias and 18 healthy donors (HDs). Out of n=213,074 CD138pos PCs, 42,717 were genotypically identified as pPCs. Compared to HDs, we detected quantitative and qualitative differences in pPCs of patients showing immunoparesis, where we showed a pro-inflammatory status, driven by specific cellular interactions with TME. Finally, we derived a "hPC signature" that, once inferred in the CoMMpass dataset, was predictive of PFS and OS. Our findings show that genotypic, single-cell identification of pPCs in PC dyscrasias has relevant pathogenic and clinical implications.

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Da Via, M. C., Lazzaroni, F., Matera, A., Marella, A., Maeda, A., De Magistris, C., Pettine, L., Fabris, S., Pioggia, S., Marchetti, A., Barbieri, M., Lonati, S., Cattaneo, A., Tornese, M., Scopetti, M., Latifinavid, N., Castellano, G., Torricelli, F., Neri, A., Fokkema, C., Cupedo, T., Lionetti, M., Passamonti, F., Bolli, N.. 2024-05-27. Genotypic identification of polyclonal plasma cells in plasma cell dyscrasias shows an aberrant single-cell phenotype with clinical implications. https://doi.org/10.1101/2024.05.26.595470

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