The mutagenic impact of melphalan in multiple myeloma Review
| Authors: | Maura, F.; Weinhold, N.; Diamond, B.; Kazandjian, D.; Rasche, L.; Morgan, G.; Landgren, O. |
| Review Title: | The mutagenic impact of melphalan in multiple myeloma |
| 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. © 2021, The Author(s), under exclusive licence to Springer Nature Limited. |
| Keywords: | cancer chemotherapy; cancer survival; treatment failure; gene mutation; lenalidomide; review; cancer recurrence; cisplatin; cancer combination chemotherapy; cancer risk; drug efficacy; drug safety; gold standard; dna synthesis; metastasis; progression free survival; apoptosis; bortezomib; multiple myeloma; bone marrow suppression; dexamethasone; melphalan; autologous stem cell transplantation; antineoplastic activity; enzyme activity; cell population; health care quality; minimal residual disease; rna synthesis; long term care; clinical decision making; hematopoietic stem cell; cancer tissue; cell expansion; health care access; drug exposure; heterochromatin; tumor engraftment; clinical trial (topic); nucleic acid base substitution; dna strand; acute myeloid leukemia; nucleotide excision repair; overall response rate; mutagenic activity; genetic damage; human; whole genome sequencing; dna alkylation; multiple myeloma cell line; apolipoprotein b mrna editing enzyme catalytic polypeptide like |
| Journal Title: | Leukemia |
| Volume: | 35 |
| Issue: | 8 |
| ISSN: | 0887-6924 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2021-08-01 |
| Start Page: | 2145 |
| End Page: | 2150 |
| Language: | English |
| DOI: | 10.1038/s41375-021-01293-3 |
| PUBMED: | 34012133 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Review -- Export Date: 1 September 2021 -- Source: Scopus |
