{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T21:41:18Z","timestamp":1790026878385,"version":"4.0.1"},"reference-count":82,"publisher":"American Society of Hematology","issue":"18","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,9,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Despite the recent progress in treatment of multiple myeloma (MM), it is still an incurable malignant disease, and we are therefore in need of new risk stratification tools that can help us to understand the disease and optimize therapy. Here we propose a new subtyping of myeloma plasma cells (PCs) from diagnostic samples, assigned by normal B-cell subset associated gene signatures (BAGS). For this purpose, we combined fluorescence-activated cell sorting and gene expression profiles from normal bone marrow (BM) Pre-BI, Pre-BII, immature, na\u00efve, memory, and PC subsets to generate BAGS for assignment of normal BM subtypes in diagnostic samples. The impact of the subtypes was analyzed in 8 available data sets from 1772 patients\u2019 myeloma PC samples. The resulting tumor assignments in available clinical data sets exhibited similar BAGS subtype frequencies in 4 cohorts from de novo MM patients across 1296 individual cases. The BAGS subtypes were significantly associated with progression-free and overall survival in a meta-analysis of 916 patients from 3 prospective clinical trials. The major impact was observed within the Pre-BII and memory subtypes, which had a significantly inferior prognosis compared with other subtypes. A multiple Cox proportional hazard analysis documented that BAGS subtypes added significant, independent prognostic information to the translocations and cyclin D classification. BAGS subtype analysis of patient cases identified transcriptional differences, including a number of differentially spliced genes. We identified subtype differences in myeloma at diagnosis, with prognostic impact and predictive potential, supporting an acquired B-cell trait and phenotypic plasticity as a pathogenetic hallmark of MM.<\/jats:p>","DOI":"10.1182\/bloodadvances.2018018564","type":"journal-article","created":{"date-parts":[[2018,9,25]],"date-time":"2018-09-25T15:45:54Z","timestamp":1537890354000},"page":"2400-2411","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":5,"title":["A multiple myeloma classification system that associates normal B-cell subset phenotypes with prognosis"],"prefix":"10.1182","volume":"2","author":[{"given":"Julie St\u00f8ve","family":"B\u00f8dker","sequence":"first","affiliation":[{"name":"Department of Haematology, Aalborg University Hospital, Aalborg, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasmus Froberg","family":"Br\u00f8ndum","sequence":"first","affiliation":[{"name":"Department of Haematology, Aalborg University Hospital, Aalborg, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Schmitz","sequence":"first","affiliation":[{"name":"Department of Haematology, Aalborg University Hospital, Aalborg, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Amanda","family":"Sch\u00f6nherz","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine, Aalborg University, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ditte Starberg","family":"Jespersen","sequence":"first","affiliation":[{"name":"Department of Haematology, Aalborg University Hospital, Aalborg, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mads","family":"S\u00f8nderk\u00e6r","sequence":"first","affiliation":[{"name":"Department of Haematology, Aalborg University Hospital, Aalborg, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Vesteghem","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine, Aalborg University, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanne","family":"Due","sequence":"first","affiliation":[{"name":"Department of Haematology, Aalborg University Hospital, Aalborg, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline Holm","family":"N\u00f8rgaard","sequence":"first","affiliation":[{"name":"Department of Haematology, Aalborg University Hospital, Aalborg, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Perez-Andres","sequence":"first","affiliation":[{"name":"Department of Haematology, Aalborg University Hospital, Aalborg, Denmark;"},{"name":"Institute of Biomedical Research of Salamanca, University of Salamanca, Salamanca, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet Kemal","family":"Samur","sequence":"first","affiliation":[{"name":"Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faith","family":"Davies","sequence":"first","affiliation":[{"name":"UAMS Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8615-6254","authenticated-orcid":false,"given":"Brian","family":"Walker","sequence":"first","affiliation":[{"name":"UAMS Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Pawlyn","sequence":"first","affiliation":[{"name":"Division of Molecular Pathology, Institute of Cancer Research, London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Kaiser","sequence":"first","affiliation":[{"name":"Division of Molecular Pathology, Institute of Cancer Research, London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Johnson","sequence":"first","affiliation":[{"name":"Division of Molecular Pathology, Institute of Cancer Research, London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uta","family":"Bertsch","sequence":"first","affiliation":[{"name":"National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemiek","family":"Broyl","sequence":"first","affiliation":[{"name":"Department of Haematology, Erasmus Medical Center, Rotterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"van Duin","sequence":"first","affiliation":[{"name":"Department of Haematology, Erasmus Medical Center, Rotterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajen","family":"Shah","sequence":"first","affiliation":[{"name":"Centre for Mathematical Sciences, University of Cambridge, Cambridge, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Preben","family":"Johansen","sequence":"first","affiliation":[{"name":"Department of Haematopathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin Agge","family":"N\u00f8rgaard","sequence":"first","affiliation":[{"name":"Department of Cardiothoracic Surgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Samworth","sequence":"first","affiliation":[{"name":"Centre for Mathematical Sciences, University of Cambridge, Cambridge, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"Sonneveld","sequence":"first","affiliation":[{"name":"Department of Haematology, Erasmus Medical Center, Rotterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmut","family":"Goldschmidt","sequence":"first","affiliation":[{"name":"National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth J.","family":"Morgan","sequence":"first","affiliation":[{"name":"UAMS Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Orfao","sequence":"first","affiliation":[{"name":"Institute of Biomedical Research of Salamanca, University of Salamanca, Salamanca, 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