ArticleThe Journal of clinical investigation2010
Mitigation of hematologic radiation toxicity in mice through pharmacological quiescence induced by CDK4/6 inhibition.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 1 of them a synthesis that pooled it.
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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
114 citing papers in PubMed, 1 synthesis or guideline pooled it, 160 citations in OpenAlex.
- Safety and efficacy profile of cyclin-dependent kinases 4/6 inhibitor palbociclib in cancer therapy: A meta-analysis of clinical trials.Cancer medicine · 2019Pooled it
- Bioequivalence of a single dose of two palbociclib formulations in healthy Chinese subjects under fasting conditions: a two-period crossover study with rabeprazole pre-treatment.Frontiers in pharmacology · 2025Trial
- Palbociclib in Solid Tumor Patients With Genomic Alterations in the cyclinD-cdk4/6-INK4a-Rb Pathway: Results From National Cancer Institute-Children's Oncology Group Pediatric Molecular Analysis for Therapy Choice Trial Arm I (APEC1621I).JCO precision oncology · 2024Trial
- Bioequivalence Study of Palbociclib Capsules in Healthy Chinese Subjects Under Fasting and Fed Conditions.Clinical drug investigation · 2022Trial
- Myelopreservation with the CDK4/6 inhibitor trilaciclib in patients with small-cell lung cancer receiving first-line chemotherapy: a phase Ib/randomized phase II trial.Annals of oncology : official journal of the European Society for Medical Oncology · 2019Trial
- Trial
- Bactericidal/permeability-increasing protein (rBPI21) and fluoroquinolone mitigate radiation-induced bone marrow aplasia and death.Science translational medicine · 2011Trial
- Disruption of CDK4/6-RARα-NF-κB axis attenuates senescence-associated inflammation and improves function during aging and following chemotherapy.Nature aging · 2026Article
- AbioRxiv : the preprint server for biology · 2026Article
- Mimicking mammalian hibernation to lock cancer cells in safe quiescence.Discover oncology · 2026Article
- Clonal hematopoiesis and its progression to myeloid neoplasms: insights into risk, biology, and therapeutic strategies.Haematologica · 2026Review
- Cell-cycle targeted cancer therapy: clinical advances, biological gaps, and the emergence of selective CDK4 inhibitors.Journal of hematology & oncology · 2026Review
- CDK4/6 inhibition mitigates chemotherapy-induced expansion of TP53-mutant clonal hematopoiesis.Nature genetics · 2026Article
- Mathematical analysis of G1/S sub-networks in hematopoietic proliferation: Sequential and lineage-specific activation.iScience · 2026Article
- Matricellular protein SMOC2 safeguards tubular integrity in acute kidney injury via integrin β3-dependent inhibition of CCND1-CDK4/6 axis.Molecular biomedicine · 2026Article
- Incidence of patient-reported fatigue developing on palbociclib and endocrine therapy for advanced HR+ HER2- breast cancer.The oncologist · 2025Article
- A novel CDK4 inhibitor for myeloid protection in chemotherapy-treated triple-negative breast Cancer.Investigational new drugs · 2025Article
- Targeting CDK4/6 in breast cancer.Experimental & molecular medicine · 2025Review
- Fluacrypyrim Protects Hematopoietic Stem and Progenitor Cells against Irradiation via Apoptosis Prevention.Molecules (Basel, Switzerland) · 2024Article
- Indole-3-carboxaldehyde ameliorates ionizing radiation-induced hematopoietic injury by enhancing hematopoietic stem and progenitor cell quiescence.Molecular and cellular biochemistry · 2024Article
54 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Total body irradiation (TBI) can induce lethal myelosuppression, due to the sensitivity of proliferating hematopoietic stem/progenitor cells (HSPCs) to ionizing radiation (IR). No effective therapy exists to mitigate the hematologic toxicities of TBI. Here, using selective and structurally distinct small molecule inhibitors of cyclin-dependent kinase 4 (CDK4) and CDK6, we have demonstrated that selective cellular quiescence increases radioresistance of human cell lines in vitro and mice in vivo. Cell lines dependent on CDK4/6 were resistant to IR and other DNA-damaging agents when treated with CDK4/6 inhibitors. In contrast, CDK4/6 inhibitors did not protect cell lines that proliferated independently of CDK4/6 activity. Treatment of wild-type mice with CDK4/6 inhibitors induced reversible pharmacological quiescence (PQ) of early HSPCs but not most other cycling cells in the bone marrow or other tissues. Selective PQ of HSPCs decreased the hematopoietic toxicity of TBI, even when the CDK4/6 inhibitor was administered several hours after TBI. Moreover, PQ at the time of administration of therapeutic IR to mice harboring autochthonous cancers reduced treatment toxicity without compromising the therapeutic tumor response. These results demonstrate an effective method to mitigate the hematopoietic toxicity of IR in mammals, which may be potentially useful after radiological disaster or as an adjuvant to anticancer therapy.
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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.