Circulating plasma cells (either polyclonal or monoclonal) as markers of aggressive Multiple Myeloma phenotype

Circulating plasma cells (either polyclonal or monoclonal) as markers of aggressive Multiple Myeloma phenotype | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Circulating plasma cells (either polyclonal or monoclonal) as markers of aggressive Multiple Myeloma phenotype Ilaria Vigliotta, Alessia Varacalli, Vincenza Solli, Barbara Taurisano, and 13 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7874753/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Multiple myeloma (MM) is a hematological neoplasm characterized by the clonal proliferation of malignant plasma cells (PCs) in the bone marrow (BM). The pathogenesis of MM is complex and multifactorial, with significant heterogeneity among patients, making risk stratification and disease monitoring difficult, often based on invasive sampling. Therefore, there is growing interest in less invasive methods such as liquid biopsy. In this study, the potential of circulating plasma cells (CPCs), including polyclonal CPCs, was evaluated as innovative biomarkers for risk stratification in 107 MM patients. Using multiparametric flow cytometry, the phenotypes of the CPCs in peripheral blood (PB) were analyzed, finding their presence in 92% of cases (monoclonal CPCs 77%, polyclonal CPCs 15%), with a median of 0.02% (range 0.002-9%). CPCs were significantly correlated with various biochemical parameters and the percentage of BM-PCs (p<0.05), indicating an association with a more aggressive phenotype even in the presence of polyclonal PCs. Genomic analyses identified recurrent mutations in key genes ( KRAS and NRAS ), potentially involved in CPCs formation. Notably, high CPCs-patients had mutation restricted to KRAS , while patients with a low amount of CPCs carried solely NRAS mutations. Lastly, comparisons between PC phenotypes in BM and PB showed significant heterogeneity, such as light chain inversion or variations in the expression of markers like CD56 and CD138, suggesting the presence of clonal heterogeneity and potential migratory predisposition. Such differences might have prognostic and therapeutic implications, and might contribute to the emergence of CPCs. Multiple Myeloma 1 Circulating tumor cells 2 Flow cytometry 3 Liquid biopsy 4 Bone marrow 5 Circulating Plasma cells 6 Mutations 7 Genomic analyses 8 Clonal heterogeneity 9 Migration 10 Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementaryVigliottaetal.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7874753","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":540171124,"identity":"26e53a21-686f-43af-87bf-02aacbda84db","order_by":0,"name":"Ilaria 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phenotype","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Multiple Myeloma 1, Circulating tumor cells 2, Flow cytometry 3, Liquid biopsy 4, Bone marrow 5, Circulating Plasma cells 6, Mutations 7, Genomic analyses 8, Clonal heterogeneity 9, Migration 10","lastPublishedDoi":"10.21203/rs.3.rs-7874753/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7874753/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eMultiple myeloma (MM) is a hematological neoplasm characterized by the clonal proliferation of malignant plasma cells (PCs) in the bone marrow (BM). The pathogenesis of MM is complex and multifactorial, with significant heterogeneity among patients, making risk stratification and disease monitoring difficult, often based on invasive sampling. Therefore, there is growing interest in less invasive methods such as liquid biopsy. In this study, the potential of circulating plasma cells (CPCs), including polyclonal CPCs, was evaluated as innovative biomarkers for risk stratification in 107 MM patients. Using multiparametric flow cytometry, the phenotypes of the CPCs in peripheral blood (PB) were analyzed, finding their presence in 92% of cases (monoclonal CPCs 77%, polyclonal CPCs 15%), with a median of 0.02% (range 0.002-9%). CPCs were significantly correlated with various biochemical parameters and the percentage of BM-PCs (p\u0026lt;0.05), indicating an association with a more aggressive phenotype even in the presence of polyclonal PCs. Genomic analyses identified recurrent mutations in key genes (\u003cem\u003eKRAS \u003c/em\u003eand\u003cem\u003eNRAS\u003c/em\u003e), potentially involved in CPCs formation. Notably, high CPCs-patients had mutation restricted to \u003cem\u003eKRAS\u003c/em\u003e, while patients with a low amount of CPCs carried solely \u003cem\u003eNRAS\u003c/em\u003e mutations. Lastly, comparisons between PC phenotypes in BM and PB showed significant heterogeneity, such as light chain inversion or variations in the expression of markers like CD56 and CD138, suggesting the presence of clonal heterogeneity and potential migratory predisposition. Such differences might have prognostic and therapeutic implications, and might contribute to the emergence of CPCs.\u003c/p\u003e","manuscriptTitle":"Circulating plasma cells (either polyclonal or monoclonal) as markers of aggressive Multiple Myeloma phenotype","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-07 19:01:24","doi":"10.21203/rs.3.rs-7874753/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"707cbef1-6d93-465d-a711-6d9773e7cec3","owner":[],"postedDate":"November 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-22T23:38:16+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-07 19:01:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7874753","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7874753","identity":"rs-7874753","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}