ArticleThe Journal of clinical investigation2017
Gene expression and mutation-guided synthetic lethality eradicates proliferating and quiescent leukemia cells.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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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
54 citing papers in PubMed, 75 citations in OpenAlex.
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- Targeted Combination of Poly(ADP-ribose) Polymerase Inhibitors and Immune Checkpoint Inhibitors Lacking Evidence of Benefit: Focus in Ovarian Cancer.International journal of molecular sciences · 2024Review
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- PARP1 Characterization as a Potential Biomarker forCancers · 2023Article
- 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
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- 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
- ABL1 kinase as a tumor suppressor in AML1-ETO and NUP98-PMX1 leukemias.Blood cancer journal · 2023Article
- Review
- Introduction of the T315I gatekeeper mutation of BCR/ABL1 into a Philadelphia chromosome-positive lymphoid leukemia cell line using the CRISPR/Cas9 system.International journal of hematology · 2022Article
- DNA Repair Genes Polymorphisms: Impact on Acute Myeloid Leukemia Patients Outcome.Asian Pacific journal of cancer prevention : APJCP · 2022Article
- Phase I Clinical Trial of DNA Methyltransferase Inhibitor Decitabine and PARP Inhibitor Talazoparib Combination Therapy in Relapsed/Refractory Acute Myeloid Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Targeting PARP proteins in acute leukemia: DNA damage response inhibition and therapeutic strategies.Journal of hematology & oncology · 2022Review
- Overcoming Resistance to Kinase Inhibitors: The Paradigm of Chronic Myeloid Leukemia.OncoTargets and therapy · 2022Review
- Review
- PARP1 as a therapeutic target in acute myeloid leukemia and myelodysplastic syndrome.Blood advances · 2021Review
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Authors and funding
32 authors at 18 institutions in 5 countries.
Funding
Abstract
Quiescent and proliferating leukemia cells accumulate highly lethal DNA double-strand breaks that are repaired by 2 major mechanisms: BRCA-dependent homologous recombination and DNA-dependent protein kinase-mediated (DNA-PK-mediated) nonhomologous end-joining, whereas DNA repair pathways mediated by poly(ADP)ribose polymerase 1 (PARP1) serve as backups. Here we have designed a personalized medicine approach called gene expression and mutation analysis (GEMA) to identify BRCA- and DNA-PK-deficient leukemias either directly, using reverse transcription-quantitative PCR, microarrays, and flow cytometry, or indirectly, by the presence of oncogenes such as BCR-ABL1. DNA-PK-deficient quiescent leukemia cells and BRCA/DNA-PK-deficient proliferating leukemia cells were sensitive to PARP1 inhibitors that were administered alone or in combination with current antileukemic drugs. In conclusion, GEMA-guided targeting of PARP1 resulted in dual cellular synthetic lethality in quiescent and proliferating immature leukemia cells, and is thus a potential approach to eradicate leukemia stem and progenitor cells that are responsible for initiation and manifestation of the disease. Further, an analysis of The Cancer Genome Atlas database indicated that this personalized medicine approach could also be applied to treat numerous solid tumors from individual patients.
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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.