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The spatio-temporal evolution of multiple myeloma from baseline to relapse-refractory states

Deciphering Multiple Myeloma evolution in the whole bone marrow is key to inform curative strategies. Here, we perform spatial-longitudinal whole-exome sequencing, including 140 samples collected from 24 Multiple Myeloma patients during up to 14 years. Applying imaging-guided sampling we observe thr...

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Main Authors: Rasche, Leo (Author) , Schinke, Carolina (Author) , Maura, Francesco (Author) , Bauer, Michael A. (Author) , Ashby, Cody (Author) , Deshpande, Shayu (Author) , Poos, Alexandra (Author) , Zangari, Maurizio (Author) , Thanendrarajan, Sharmilan (Author) , Davies, Faith E. (Author) , Walker, Brian A. (Author) , Barlogie, Bart (Author) , Landgren, Ola (Author) , Morgan, Gareth J. (Author) , van Rhee, Frits (Author) , Weinhold, Niels (Author)
Format: Article (Journal)
Language:English
Published: 03 August 2022
In: Nature Communications
Year: 2022, Volume: 13, Pages: 1-13
ISSN:2041-1723
DOI:10.1038/s41467-022-32145-y
Online Access:Resolving-System, kostenfrei, Volltext: https://doi.org/10.1038/s41467-022-32145-y
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41467-022-32145-y
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Author Notes:Leo Rasche, Carolina Schinke, Francesco Maura, Michael A. Bauer, Cody Ashby, Shayu Deshpande, Alexandra M. Poos, Maurizio Zangari, Sharmilan Thanendrarajan, Faith E. Davies, Brian A. Walker, Bart Barlogie, Ola Landgren, Gareth J. Morgan, Frits van Rhee & Niels Weinhold
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Summary:Deciphering Multiple Myeloma evolution in the whole bone marrow is key to inform curative strategies. Here, we perform spatial-longitudinal whole-exome sequencing, including 140 samples collected from 24 Multiple Myeloma patients during up to 14 years. Applying imaging-guided sampling we observe three evolutionary patterns, including relapse driven by a single-cell expansion, competing/co-existing sub-clones, and unique sub-clones at distinct locations. While we do not find the unique relapse sub-clone in the baseline focal lesion(s), we show a close phylogenetic relationship between baseline focal lesions and relapse disease, highlighting focal lesions as hotspots of tumor evolution. In patients with ≥3 focal lesions on positron-emission-tomography at diagnosis, relapse is driven by multiple distinct sub-clones, whereas in other patients, a single-cell expansion is typically seen (p < 0.01). Notably, we observe resistant sub-clones that can be hidden over years, suggesting that a prerequisite for curative therapies would be to overcome not only tumor heterogeneity but also dormancy.
Item Description:Gesehen am 01.09.2022
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-022-32145-y

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