| Title: | Ex vivo drug response heterogeneity reveals personalized therapeutic strategies for patients with multiple myeloma |
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| Authors: | ID Kropivšek, Klara (Author)
ID Kachel, Paul (Author)
ID Goetze, Sandra (Author)
ID Wegmann, Rebekka (Author)
ID Festl, Yasmin (Author)
ID Severin, Yannik (Author)
ID Hale, Benjamin D. (Author)
ID Mena, Julien (Author)
ID Van Drogen, Audrey (Author)
ID Dietliker, Nadja (Author), et al. |
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| Files: |  https://www.nature.com/articles/s43018-023-00544-9
 s43018-023-00544-9.pdf (10,16 MB)
MD5: E2F6E4CA36F8CF94419186DB65374071
https://www.nature.com/articles/s43018-023-00544-9.pdf
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| Language: | English |
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| Work type: | Unknown |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: | UNG - University of Nova Gorica
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| Abstract: | Abstract
Multiple myeloma (MM) is a plasma cell malignancy defined by complex genetics and extensive patient heterogeneity. Despite a growing arsenal of approved therapies, MM remains incurable and in need of guidelines to identify effective personalized treatments. Here, we survey the ex vivo drug and immunotherapy sensitivities across 101 bone marrow samples from 70 patients with MM using multiplexed immunofluorescence, automated microscopy and deep-learning-based single-cell phenotyping. Combined with sample-matched genetics, proteotyping and cytokine profiling, we map the molecular regulatory network of drug sensitivity, implicating the DNA repair pathway and EYA3 expression in proteasome inhibitor sensitivity and major histocompatibility complex class II expression in the response to elotuzumab. Globally, ex vivo drug sensitivity associated with bone marrow microenvironmental signatures reflecting treatment stage, clonality and inflammation. Furthermore, ex vivo drug sensitivity significantly stratified clinical treatment responses, including to immunotherapy. Taken together, our study provides molecular and actionable insights into diverse treatment strategies for patients with MM. |
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| Keywords: | ultiple myeloma, precision medicine, ex-vivo, pharmacoscopy, proteotyping, oncology, hematology, microscopy, drug score |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Publication date: | 01.05.2023 |
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| Year of publishing: | 2023 |
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| Number of pages: | str. 734-753 |
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| Numbering: | Vol. 52, no. 5 |
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| COBISS.SI-ID: | 214560259  |
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| UDC: | 616-006 |
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| ISSN on article: | 2662-1347 |
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| eISSN: | 2662-1347 |
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| DOI: | 10.1038/s43018-023-00544-9 |
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| NUK URN: | URN:SI:UNG:REP:TRKKULPQ |
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| Publication date in RUNG: | 11.11.2024 |
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| Views: | 85 |
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| Downloads: | 0 |
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