ArticleOncogene2013
Targeting abnormal DNA double-strand break repair in tyrosine kinase inhibitor-resistant chronic myeloid leukemias.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
62 citing papers in PubMed, 108 citations in OpenAlex.
- Emerging insights into alternative end‑joining: Mechanisms, genome instability and therapeutic opportunities in cancer (Review).International journal of oncology · 2025Review
- Joining of DNA breaks- interplay between DNA ligases and poly (ADP-ribose) polymerases.DNA repair · 2025Review
- Harnessing transcriptional regulation of alternative end-joining to predict cancer treatment.NAR cancer · 2025Article
- Impact of DNA ligase inhibition on the nick sealing of polβ nucleotide insertion products at the downstream steps of base excision repair pathway.Mutagenesis · 2024Article
- HDAC8 Enhances the Function of HIF-2α by Deacetylating ETS1 to Decrease the Sensitivity of TKIs in ccRCC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- PARG is essential for Polθ-mediated DNA end-joining by removing repressive poly-ADP-ribose marks.Nature communications · 2024Article
- Antileukemic potential of methylated indolequinone MAC681 through immunogenic necroptosis and PARP1 degradation.Biomarker research · 2024Article
- Microhomology-mediated repair machinery and its relationship with HPV-mediated oncogenesis.Journal of medical virology · 2024Review
- Improving CRISPR-Cas9 directed faithful transgene integration outcomes by reducing unwanted random DNA integration.Journal of biomedical science · 2024Article
- Mammalian DNA ligases; roles in maintaining genome integrity.Journal of molecular biology · 2024Review
- Targeting the DNA damage response in hematological malignancies.Frontiers in oncology · 2024Review
- Article
- Targeting Poly(ADP)ribose polymerase in BCR/ABL1-positive cells.Scientific reports · 2023Article
- Synergistic effect of combined PI3 kinase inhibitor and PARP inhibitor treatment on BCR/ABL1-positive acute lymphoblastic leukemia cells.International journal of hematology · 2023Article
- Chromosomal Instability in Chronic Myeloid Leukemia: Mechanistic Insights and Effects.Cancers · 2022Review
- Review
- PARP1 as a therapeutic target in acute myeloid leukemia and myelodysplastic syndrome.Blood advances · 2021Review
- Involvement of classic and alternative non-homologous end joining pathways in hematologic malignancies: targeting strategies for treatment.Experimental hematology & oncology · 2021Review
- Review
- Resistance to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia-From Molecular Mechanisms to Clinical Relevance.Cancers · 2021Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Resistance to imatinib (IM) and other tyrosine kinase inhibitors (TKI)s is an increasing problem in leukemias caused by expression of BCR-ABL1. As chronic myeloid leukemia (CML) cell lines expressing BCR-ABL1 utilize an alternative non-homologous end-joining pathway (ALT NHEJ) to repair DNA double-strand breaks (DSB)s, we asked whether this repair pathway is a novel therapeutic target in TKI-resistant disease. Notably, the steady state levels of two ALT NHEJ proteins, poly-(ADP-ribose) polymerase 1 (PARP1) and DNA ligase IIIα, were increased in the BCR-ABL1-positive CML cell line K562 and, to a greater extent, in its imatinib-resistant (IMR) derivative. Incubation of these cell lines with a combination of DNA ligase and PARP inhibitors inhibited ALT NHEJ and selectively decreased survival with the effect being greater in the IMR derivative. Similar results were obtained with TKI-resistant derivatives of two hematopoietic cell lines that had been engineered to stably express BCR-ABL1. Together our results show that the sensitivity of cell lines expressing BCR-ABL1 to the combination of DNA ligase and PARP inhibitors correlates with the steady state levels of PARP1 and DNA ligase IIIα, and ALT NHEJ activity. Importantly, analysis of clinical samples from CML patients confirmed that the expression levels of PARP1 and DNA ligase IIIα correlated with the sensitivity to the DNA repair inhibitor combination. Thus, the expression levels of PARP1 and DNA ligase IIIα serve as biomarkers to identify a subgroup of CML patients who may be candidates for therapies that target the ALT NHEJ pathway when treatment with TKIs has failed.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.