{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T05:07:36Z","timestamp":1789276056720,"version":"build-2803163510"},"reference-count":86,"publisher":"American Society of Hematology","issue":"26","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,6,26]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Multiple myeloma (MM) is driven by clonal plasma cell (cPC)\u2013intrinsic factors and changes in the tumor microenvironment (TME). To investigate whether residual polyclonal PCs (pPCs) are disrupted, single-cell (sc) RNA sequencing (scRNA-seq) and sc B-cell receptor analysis were applied in a cohort of 46 samples with PC dyscrasias and 21 healthy donors (HDs). Of 234\u2009789 PCs, 64\u2009432 were genotypically identified as pPCs with frequencies decreasing over different disease stages, from 23.66% in monoclonal gammopathy of undetermined significance to 3.23% in MMs (P = .00012). Both cPCs and pPCs had a comparable expression of typical lineage markers (ie, CD38 and CD138), whereas others were more variable (CD27 and ITGB7). Only cPCs overexpressed oncogenes (eg, CCND1\/2 and NSD2), but CCND3 was often expressed in pPCs. B-cell maturation antigen was expressed on both pPCs and cPCs, whereas GPRC5D was mostly upregulated in cPCs with implications for on-target, off-tumor activity of targeted immunotherapies. In comparison with HDs, pPCs from patients showed upregulated autophagy and disrupted interaction with TME. Importantly, interferon-related pathways were significantly enriched in pPCs from patients vs HDs (adjusted P &amp;lt; .05) showing an inflamed phenotype affecting genotypically normal PCs. The function of pPCs was consequently affected and correlated with immunoparesis, driven by disrupted cellular interactions with TME. Leveraging our scRNA-seq data, we derived a \u201chealthy PC signature\u201d that could be applied to bulk transcriptomics from the CoMMpass data set and predicted significantly better progression-free survival and overall survival (log-rank P &amp;lt; .05 for both). Our findings show that genotypic sc identification of pPCs in PC dyscrasias has relevant pathogenic and clinical implications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2024025643","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T12:17:28Z","timestamp":1740572248000},"page":"3124-3138","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":14,"title":["Aberrant single-cell phenotype and clinical implications of genotypically defined polyclonal plasma cells in myeloma"],"prefix":"10.1182","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5396-6584","authenticated-orcid":false,"given":"Matteo Claudio","family":"Da Vi\u00e0","sequence":"first","affiliation":[{"name":"1Hematology Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, 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