A multiple myeloma classification system that associates normal B-cell subset phenotypes with prognosis
Autor: | Charlotte Pawlyn, Hanne Due, Mehmet Kemal Samur, Annemiek Broyl, Charles Vesteghem, Ditte Starberg Jespersen, Julie Støve Bødker, Uta Bertsch, Faith E. Davies, Anna Amanda Schönherz, Nikhil C. Munshi, Martin Agge Nørgaard, Martin Perez-Andres, Alberto Orfao, Gareth J. Morgan, Rasmus Froberg Brøndum, Tarec Christoffer El-Galaly, Martin Kaiser, Alexander Schmitz, Brian A Walker, Hans Erik Johnson, Pieter Sonneveld, Martin Bøgsted, Rajen D. Shah, Hartmut Goldschmidt, Mads Sønderkær, Karen Dybkær, Richard J. Samworth, Mark van Duin, Preben Johansen, Caroline Holm Nørgaard, David W. Johnson |
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Přispěvatelé: | Hematology, Walker, Brian [0000-0002-8615-6254], Apollo - University of Cambridge Repository |
Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty B-Lymphocyte Subsets Disease Immunophenotyping 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Biomarkers Tumor Humans B cell Survival analysis Multiple myeloma business.industry Gene Expression Profiling Hematology medicine.disease Prognosis Survival Analysis Subtyping Gene expression profiling 030104 developmental biology medicine.anatomical_structure Phenotype Erratum business Multiple Myeloma Transcriptome 030215 immunology |
Zdroj: | Bødker, J S, Brøndum, R F, Schmitz, A, Schönherz, A A, Jespersen, D S, Sønderkær, M, Vesteghem, C, Due, H, Nørgaard, C H, Perez-Andres, M, Samur, M K, Davies, F, Walker, B, Pawlyn, C, Kaiser, M, Johnson, D, Bertsch, U, Broyl, A, van Duin, M, Shah, R, Johansen, P, Nørgaard, M A, Samworth, R J, Sonneveld, P, Goldschmidt, H, Morgan, G J, Orfao, A, Munshi, N, Johnsen, H E, El-Galaly, T, Dybkær, K & Bøgsted, M 2018, ' A multiple myeloma classification system that associates normal B-cell subset phenotypes with prognosis ', Blood advances, vol. 2, no. 18, pp. 2400-2411 . https://doi.org/10.1182/bloodadvances.2018018564 Blood advances, 2(18), 2400-2411. American Society of Hematology Bødker, J S, Brøndum, R F, Schmitz, A, Schönherz, A A, Jespersen, D S, Sønderkær, M, Vesteghem, C, Due, H, Nørgaard, C H, Perez-Andres, M, Samur, M K, Davies, F, Walker, B, Pawlyn, C, Kaiser, M, Johnson, D, Bertsch, U, Broyl, A, van Duin, M, Shah, R, Johansen, P, Nørgaard, M A, Samworth, R J, Sonneveld, P, Goldschmidt, H, Morgan, G J, Orfao, A, Munshi, N, Johnson, H E, El-Galaly, T, Dybkær, K & Bøgsted, M 2018, ' A multiple myeloma classification system that associates normal B-cell subset phenotypes with prognosis ' Blood Advances, vol. 2, no. 18, pp. 2400-2411 . https://doi.org/10.1182/bloodadvances.2018018564 |
ISSN: | 2473-9529 |
Popis: | 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. |
Databáze: | OpenAIRE |
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