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dc.contributor.authorBødker, JSen_US
dc.contributor.authorBrøndum, RFen_US
dc.contributor.authorSchmitz, Aen_US
dc.contributor.authorSchönherz, AAen_US
dc.contributor.authorJespersen, DSen_US
dc.contributor.authorSønderkær, Men_US
dc.contributor.authorVesteghem, Cen_US
dc.contributor.authorDue, Hen_US
dc.contributor.authorNørgaard, CHen_US
dc.contributor.authorPerez-Andres, Men_US
dc.contributor.authorSamur, MKen_US
dc.contributor.authorDavies, Fen_US
dc.contributor.authorWalker, Ben_US
dc.contributor.authorPawlyn, Cen_US
dc.contributor.authorKaiser, Men_US
dc.contributor.authorJohnson, Den_US
dc.contributor.authorBertsch, Uen_US
dc.contributor.authorBroyl, Aen_US
dc.contributor.authorvan Duin, Men_US
dc.contributor.authorShah, Ren_US
dc.contributor.authorJohansen, Pen_US
dc.contributor.authorNørgaard, MAen_US
dc.contributor.authorSamworth, RJen_US
dc.contributor.authorSonneveld, Pen_US
dc.contributor.authorGoldschmidt, Hen_US
dc.contributor.authorMorgan, GJen_US
dc.contributor.authorOrfao, Aen_US
dc.contributor.authorMunshi, Nen_US
dc.contributor.authorJohnson, HEen_US
dc.contributor.authorEl-Galaly, Ten_US
dc.contributor.authorDybkær, Ken_US
dc.contributor.authorBøgsted, Men_US
dc.coverage.spatialUnited Statesen_US
dc.identifier.citationBlood Adv, 2018, 2 (18), pp. 2400 - 2411en_US
dc.description.abstractDespite 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, naïve, 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' 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.en_US
dc.format.extent2400 - 2411en_US
dc.titleA multiple myeloma classification system that associates normal B-cell subset phenotypes with prognosis.en_US
dc.typeJournal Article
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfBlood Adven_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Translational Cancer Discovery
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Myeloma Group
pubs.embargo.termsNot knownen_US
icr.researchteamTranslational Cancer Discoveryen_US
icr.researchteamMyeloma Groupen_US
dc.contributor.icrauthorJohnson, Daviden_US
dc.contributor.icrauthorKaiser, Martinen_US
dc.contributor.icrauthorPawlyn, Charlotteen_US

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