ArticlePloS one2015
Deregulation of DNA double-strand break repair in multiple myeloma: implications for genome stability.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Mechanisms of traditional Chinese medicine overcoming of radiotherapy resistance in breast cancer.Frontiers in oncology · 2024Pooled it
- Signals in Peripheral Blood: Tracking Redox Status and DNA Damage Response During the Progression of Multiple Myeloma.International journal of molecular sciences · 2026Article
- Breaking the Balance: Baseline Oxidative Stress and DNA Repair Capacity in Multiple Myeloma Therapy.Cancers · 2026Article
- Synergistic Effects of DNA-PKcs Inhibition and Radiotherapy in Esophageal Squamous Cell Carcinoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Three-dimensional-bioprinted stiff matrix triggers PDAC radioresistance through histone H3 lysine 18 lactylation (H3K18la) potentiates RAD51 activation.Regenerative biomaterials · 2026Article
- DNA Damage Response and Redox Status in the Resistance of Multiple Myeloma Cells to Genotoxic Treatment.International journal of molecular sciences · 2025Article
- Polymerase theta inhibition impairs tumor growth and amplifies melphalan-induced DNA damage in multiple myeloma.Journal of translational medicine · 2025Article
- Germline predisposition in multiple myeloma.iScience · 2025Article
- TRIM33 loss in multiple myeloma is associated with genomic instability and sensitivity to PARP inhibitors.Scientific reports · 2024Article
- Molecular mechanisms of tumor resistance to radiotherapy.Molecular cancer · 2023Review
- Ku-DNA binding inhibitors modulate the DNA damage response in response to DNA double-strand breaks.NAR cancer · 2023Article
- DNA Damage Response Alterations in Ovarian Cancer: From Molecular Mechanisms to Therapeutic Opportunities.Cancers · 2023Review
- The Role of DNA Repair in Genomic Instability of Multiple Myeloma.International journal of molecular sciences · 2022Review
- Article
- THZ531 Induces a State of BRCAness in Multiple Myeloma Cells: Synthetic Lethality with Combination Treatment of THZ 531 with DNA Repair Inhibitors.International journal of molecular sciences · 2022Article
- Review
- Review
- Involvement of classic and alternative non-homologous end joining pathways in hematologic malignancies: targeting strategies for treatment.Experimental hematology & oncology · 2021Review
- Targeting the Interplay between HDACs and DNA Damage Repair for Myeloma Therapy.International journal of molecular sciences · 2021Review
- TRIM44 mediated p62 deubiquitination enhances DNA damage repair by increasing nuclear FLNA and 53BP1 expression.Oncogene · 2021Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple myeloma (MM) is a hematological malignancy characterized by frequent chromosome abnormalities. However, the molecular basis for this genome instability remains unknown. Since both impaired and hyperactive double strand break (DSB) repair pathways can result in DNA rearrangements, we investigated the functionality of DSB repair in MM cells. Repair kinetics of ionizing-radiation (IR)-induced DSBs was similar in MM and normal control lymphoblastoid cell lines, as revealed by the comet assay. However, four out of seven MM cell lines analyzed exhibited a subset of persistent DSBs, marked by γ-H2AX and Rad51 foci that elicited a prolonged G2/M DNA damage checkpoint activation and hypersensitivity to IR, especially in the presence of checkpoint inhibitors. An analysis of the proteins involved in DSB repair in MM cells revealed upregulation of DNA-PKcs, Artemis and XRCC4, that participate in non-homologous end joining (NHEJ), and Rad51, involved in homologous recombination (HR). Accordingly, activity of both NHEJ and HR were elevated in MM cells compared to controls, as determined by in vivo functional assays. Interestingly, levels of proteins involved in a highly mutagenic, translocation-promoting, alternative NHEJ subpathway (Alt-NHEJ) were also increased in all MM cell lines, with the Alt-NHEJ protein DNA ligase IIIα, also overexpressed in several plasma cell samples isolated from MM patients. Overactivation of the Alt-NHEJ pathway was revealed in MM cells by larger deletions and higher sequence microhomology at repair junctions, which were reduced by chemical inhibition of the pathway. Taken together, our results uncover a deregulated DSB repair in MM that might underlie the characteristic genome instability of the disease, and could be therapeutically exploited.
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