ArticleBlood2023
DNA polymerase θ protects leukemia cells from metabolically induced DNA damage.
Article in Blood, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 14 citations in OpenAlex.
- DNA polymerase theta (Polθ): a novel candidate for targeted cancer therapy.Cancer biology & therapy · 2026Review
- Aldehyde Detoxification in Cancer: Metabolic Guardians of the Genome.Biomolecules · 2026Review
- Polθ activity modulates sensitivity to standard therapies in DNMT3A-deficient leukemia.Cell reports. Medicine · 2026Article
- Polymerase theta inhibition impairs tumor growth and amplifies melphalan-induced DNA damage in multiple myeloma.Journal of translational medicine · 2025Article
- Article
- POLQ mediated end-joining promotes DNA damage tolerance in neuroblastoma.Translational oncology · 2025Article
- Amphiphilic Oligonucleotide Derivatives as a Tool to Study DNA Repair Proteins.International journal of molecular sciences · 2025Article
- Star wars against leukemia: attacking the clones.Leukemia · 2024Review
- Targeting the DNA damage response in cancer.MedComm · 2024Review
- Structural basis for a Polθ helicase small-molecule inhibitor revealed by cryo-EM.Nature communications · 2024Article
- PARG is essential for Polθ-mediated DNA end-joining by removing repressive poly-ADP-ribose marks.Nature communications · 2024Article
- Clinical Validation of the Somatic FANCD2 Mutation (c.2022-5C>T) as a Novel Molecular Biomarker for Early Disease Progression in Chronic Myeloid Leukemia: A Case-Control Study.Hematology reports · 2024Article
- Adaptive use of error-prone DNA polymerases provides flexibility in genome replication during tumorigenesis.Cancer science · 2024Review
- DNA damage response genes as biomarkers of therapeutic outcomes in acute myeloid leukemia patients.Leukemia · 2024Article
- Article
- Application and research progress of single cell sequencing technology in leukemia.Frontiers in oncology · 2024Review
- Simultaneous Targeting of DNA Polymerase Theta and PARP1 or RAD52 Triggers Dual Synthetic Lethality in Homologous Recombination-Deficient Leukemia Cells.Molecular cancer research : MCR · 2023Article
- Genotoxic aldehyde stress prematurely ages hematopoietic stem cells in a p53-driven manner.Molecular cell · 2023Article
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
38 authors at 16 institutions in 4 countries.
Funding
Abstract
Leukemia cells accumulate DNA damage, but altered DNA repair mechanisms protect them from apoptosis. We showed here that formaldehyde generated by serine/1-carbon cycle metabolism contributed to the accumulation of toxic DNA-protein crosslinks (DPCs) in leukemia cells, especially in driver clones harboring oncogenic tyrosine kinases (OTKs: FLT3(internal tandem duplication [ITD]), JAK2(V617F), BCR-ABL1). To counteract this effect, OTKs enhanced the expression of DNA polymerase theta (POLθ) via ERK1/2 serine/threonine kinase-dependent inhibition of c-CBL E3 ligase-mediated ubiquitination of POLθ and its proteasomal degradation. Overexpression of POLθ in OTK-positive cells resulted in the efficient repair of DPC-containing DNA double-strand breaks by POLθ-mediated end-joining. The transforming activities of OTKs and other leukemia-inducing oncogenes, especially of those causing the inhibition of BRCA1/2-mediated homologous recombination with and without concomitant inhibition of DNA-PK-dependent nonhomologous end-joining, was abrogated in Polq-/- murine bone marrow cells. Genetic and pharmacological targeting of POLθ polymerase and helicase activities revealed that both activities are promising targets in leukemia cells. Moreover, OTK inhibitors or DPC-inducing drug etoposide enhanced the antileukemia effect of POLθ inhibitor in vitro and in vivo. In conclusion, we demonstrated that POLθ plays an essential role in protecting leukemia cells from metabolically induced toxic DNA lesions triggered by formaldehyde, and it can be targeted to achieve a therapeutic effect.
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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.