ArticleScience signaling2016
Targeting the kinase activities of ATR and ATM exhibits antitumoral activity in mouse models of MLL-rearranged AML.
Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Biomarkers in Ataxia-Telangiectasia: a Systematic Review.Journal of neurology · 2025Pooled it
- ATM inhibition increases the anti-tumor efficacy of radium-223 (Ra-223) against prostate cancer bone metastasis in preclinical models.JBMR plus · 2025Article
- Energy Deficiency-Induced ATG4B Nuclear Translocation Inhibits PRMT1-Mediated DNA Repair and Promotes Leukemia Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- WNK1 signalling regulates amino acid transport and mTORC1 activity to sustain acute myeloid leukaemia growth.Nature communications · 2025Article
- An Alternatively Spliced Gain-of-Function NT5C2 Isoform Contributes to Chemoresistance in Acute Lymphoblastic Leukemia.Cancer research · 2024Article
- The DNA damage-independent ATM signalling maintains CBP/DOT1L axis in MLL rearranged acute myeloid leukaemia.Oncogene · 2024Article
- Targeting the DNA damage response in hematological malignancies.Frontiers in oncology · 2024Review
- Modelling acute myeloid leukemia (AML): What's new? A transition from the classical to the modern.Drug delivery and translational research · 2023Review
- Selective Inhibition of ATM-dependent Double-strand Break Repair and Checkpoint Control Synergistically Enhances the Efficacy of ATR Inhibitors.Molecular cancer therapeutics · 2023Article
- Phosphorylation stabilized TET1 acts as an oncoprotein and therapeutic target in B cell acute lymphoblastic leukemia.Science translational medicine · 2023Article
- Resistance to DNA repair inhibitors in cancer.Molecular oncology · 2022Review
- Therapeutic targeting of ATR in alveolar rhabdomyosarcoma.Nature communications · 2022Article
- Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress.Nature cancer · 2022Article
- Article
- Involvement of classic and alternative non-homologous end joining pathways in hematologic malignancies: targeting strategies for treatment.Experimental hematology & oncology · 2021Review
- Molecular basis of human ATM kinase inhibition.Nature structural & molecular biology · 2021Article
- A chemical screen for modulators of mRNA translation identifies a distinct mechanism of toxicity for sphingosine kinase inhibitors.PLoS biology · 2021Article
- Targeting acute myeloid leukemia dependency on VCP-mediated DNA repair through a selective second-generation small-molecule inhibitor.Science translational medicine · 2021Article
- Concerted roles of PTEN and ATM in controlling hematopoietic stem cell fitness and dormancy.The Journal of clinical investigation · 2021Article
- Anlotinib suppresses MLL-rearranged acute myeloid leukemia cell growth by inhibiting SETD1A/AKT-mediated DNA damage response.American journal of translational research · 2021Article
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
Abstract
Among the various subtypes of acute myeloid leukemia (AML), those with chromosomal rearrangements of the MLL oncogene (AML-MLL) have a poor prognosis. AML-MLL tumor cells are resistant to current genotoxic therapies because of an attenuated response by p53, a protein that induces cell cycle arrest and apoptosis in response to DNA damage. In addition to chemicals that damage DNA, efforts have focused on targeting DNA repair enzymes as a general chemotherapeutic approach to cancer treatment. Here, we found that inhibition of the kinase ATR, which is the primary sensor of DNA replication stress, induced chromosomal breakage and death of mouse AML(MLL) cells (with an MLL-ENL fusion and a constitutively active N-RAS independently of p53. Moreover, ATR inhibition as a single agent exhibited antitumoral activity, both reducing tumor burden after establishment and preventing tumors from growing, in an immunocompetent allograft mouse model of AML(MLL) and in xenografts of a human AML-MLL cell line. We also found that inhibition of ATM, a kinase that senses DNA double-strand breaks, also promoted the survival of the AML(MLL) mice. Collectively, these data indicated that ATR or ATM inhibition represent potential therapeutic strategies for the treatment of AML, especially MLL-driven leukemias.
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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.