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Clonal evolution after treatment pressure in multiple myeloma: heterogenous genomic aberrations and transcriptomic convergence

Authors :
Kristine Misund
Davine Hofste op Bruinink
Eivind Coward
Remco M. Hoogenboezem
Even Holth Rustad
Mathijs A. Sanders
Morten Rye
Anne-Marit Sponaas
Bronno van der Holt
Sonja Zweegman
Eivind Hovig
Leonardo A. Meza-Zepeda
Anders Sundan
Ola Myklebost
Pieter Sonneveld
Anders Waage
Hematology
CCA - Cancer Treatment and quality of life
Anatomy and neurosciences
Source :
Leukemia, 36(7), 1887-1897. Nature Publishing Group, Leukemia, Misund, K, Hofste op Bruinink, D, Coward, E, Hoogenboezem, R M, Rustad, E H, Sanders, M A, Rye, M, Sponaas, A-M, van der Holt, B, Zweegman, S, Hovig, E, Meza-Zepeda, L A, Sundan, A, Myklebost, O, Sonneveld, P & Waage, A 2022, ' Clonal evolution after treatment pressure in multiple myeloma : heterogenous genomic aberrations and transcriptomic convergence ', Leukemia, vol. 36, no. 7, pp. 1887-1897 . https://doi.org/10.1038/s41375-022-01597-y
Publication Year :
2022

Abstract

We investigated genomic and transcriptomic changes in paired tumor samples of 29 in-house multiple myeloma (MM) patients and 28 patients from the MMRF CoMMpass study before and after treatment. A change in clonal composition was found in 46/57 (82%) of patients, and single-nucleotide variants (SNVs) increased from median 67 to 86. The highest increase in prevalence of genetic aberrations was found in RAS genes (60% to 72%), amp1q21 (18% to 35%), and TP53 (9% to 18%). The SBS-MM1 mutation signature was detected both in patients receiving high and low dose melphalan. A total of 2589 genes were differentially expressed between early and late samples (FDR XPO1 and ABC transporters. Our study demonstrates a transcriptomic convergence of pathways supporting increased proliferation and metabolism during disease progression in MM.

Details

Language :
English
ISSN :
08876924
Database :
OpenAIRE
Journal :
Leukemia, 36(7), 1887-1897. Nature Publishing Group, Leukemia, Misund, K, Hofste op Bruinink, D, Coward, E, Hoogenboezem, R M, Rustad, E H, Sanders, M A, Rye, M, Sponaas, A-M, van der Holt, B, Zweegman, S, Hovig, E, Meza-Zepeda, L A, Sundan, A, Myklebost, O, Sonneveld, P & Waage, A 2022, ' Clonal evolution after treatment pressure in multiple myeloma : heterogenous genomic aberrations and transcriptomic convergence ', Leukemia, vol. 36, no. 7, pp. 1887-1897 . https://doi.org/10.1038/s41375-022-01597-y
Accession number :
edsair.doi.dedup.....3d2627cfde29a6112111f63bd8442dc5
Full Text :
https://doi.org/10.1038/s41375-022-01597-y