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The mutagenic impact of melphalan in multiple myeloma

Maura, Francesco, Weinhold, Niels, Diamond, Benjamin, Kazandjian, Dickran, Rasche, Leo, Morgan, Gareth, Landgren, Ola·2021·Leukemia
DOI 10.1038/s41375-021-01293-3
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Abstract

The introduction of whole genome and exome sequencing partnered with advanced bioinformatic pipelines has allowed the comprehensive characterization of mutational processes (i.e., mutational signatures) in individual cancer patients. Studies focusing on multiple myeloma have defined several mutational processes, including a recently identified mutational signature (called "SBS-MM1") directly caused by exposure to high-dose melphalan (i.e., autologous stem cell transplant). High-dose melphalan exposure increases both the overall and nonsynonymous mutational burden detected between diagnosis and relapse by ~10-20%. Nevertheless, most of these mutations are acquired within the heterochromatin and late-replicating regions, rarely involving key myeloma driver genes. In this review, we summarize key studies that made this discovery possible, and we discuss potential clinical implications.

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Citations

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Research works printed but not linked: 31

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Metadata

Authors
Maura, F., Weinhold, N., Diamond, B., Kazandjian, D., Rasche, L., Morgan, G., & Landgren, O.
Venue
Leukemia
Publisher
Springer Science and Business Media LLC
Published
2021-05-19
Volume
35
Issue
8
Pages
2145-2150
ISSN
  • 0887-6924
  • 1476-5551
DOI
10.1038/s41375-021-01293-3
Cited by
60
References
4
Language
en
Licence

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