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A multiple myeloma classification system that associates normal B-cell subset phenotypes with prognosis.


ABSTRACT: 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, 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.

SUBMITTER: Bodker JS 

PROVIDER: S-EPMC6156884 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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A multiple myeloma classification system that associates normal B-cell subset phenotypes with prognosis.

Bødker Julie Støve JS   Brøndum Rasmus Froberg RF   Schmitz Alexander A   Schönherz Anna Amanda AA   Jespersen Ditte Starberg DS   Sønderkær Mads M   Vesteghem Charles C   Due Hanne H   Nørgaard Caroline Holm CH   Perez-Andres Martin M   Samur Mehmet Kemal MK   Davies Faith F   Walker Brian B   Pawlyn Charlotte C   Kaiser Martin M   Johnson David D   Bertsch Uta U   Broyl Annemiek A   van Duin Mark M   Shah Rajen R   Johansen Preben P   Nørgaard Martin Agge MA   Samworth Richard J RJ   Sonneveld Pieter P   Goldschmidt Hartmut H   Morgan Gareth J GJ   Orfao Alberto A   Munshi Nikhil N   Johnson Hans Erik HE   El-Galaly Tarec T   Dybkær Karen K   Bøgsted Martin M  

Blood advances 20180901 18


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 <u>g</u>ene signatures (BAGS). For this purpose, we combined fluorescence-activated cell sorting and gene expression profiles from  ...[more]

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