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

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 Rhee and Niels Weinhold ()
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Leo Rasche: University of Arkansas for Medical Sciences
Carolina Schinke: University of Arkansas for Medical Sciences
Francesco Maura: University of Miami
Michael A. Bauer: University of Arkansas for Medical Sciences
Cody Ashby: University of Arkansas for Medical Sciences
Shayu Deshpande: University of Arkansas for Medical Sciences
Alexandra M. Poos: University Hospital of Heidelberg
Maurizio Zangari: University of Arkansas for Medical Sciences
Sharmilan Thanendrarajan: University of Arkansas for Medical Sciences
Faith E. Davies: New York University Langone Health
Brian A. Walker: Indiana University
Bart Barlogie: University of Arkansas for Medical Sciences
Ola Landgren: University of Miami
Gareth J. Morgan: New York University Langone Health
Frits Rhee: University of Arkansas for Medical Sciences
Niels Weinhold: University of Arkansas for Medical Sciences

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract 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

Date: 2022
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DOI: 10.1038/s41467-022-32145-y

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