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

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Date
2022-08-03
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American English
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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.

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Rasche, L., Schinke, C., Maura, F., Bauer, M. A., Ashby, C., Deshpande, S., Poos, A. M., Zangari, M., Thanendrarajan, S., Davies, F. E., Walker, B. A., Barlogie, B., Landgren, O., Morgan, G. J., van Rhee, F., & Weinhold, N. (2022). The spatio-temporal evolution of multiple myeloma from baseline to relapse-refractory states. Nature Communications, 13(1), 4517. https://doi.org/10.1038/s41467-022-32145-y
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Nature Communications
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