ArticleLeukemia2014
Efficacy of cyclin-dependent-kinase 9 inhibitors in a murine model of mixed-lineage leukemia.
Article in Leukemia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
26 citing papers in PubMed, 36 citations in OpenAlex.
- CDK9 and hematologic malignancies: pioneering novel therapeutic approaches.Clinical and experimental medicine · 2026Review
- Flavopiridol: a promising cyclin-dependent kinase inhibitor in cancer treatment.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- The Pharmacological Implications of Flavopiridol: An Updated Overview.Molecules (Basel, Switzerland) · 2023Review
- Unraveling MYC's Role in Orchestrating Tumor Intrinsic and Tumor Microenvironment Interactions Driving Tumorigenesis and Drug Resistance.Pathophysiology : the official journal of the International Society for Pathophysiology · 2023Review
- Targeting OXPHOS de novo purine synthesis as the nexus ofScience advances · 2022Article
- Targeting transcription cycles in cancer.Nature reviews. Cancer · 2022Review
- Review
- CDK9: A Comprehensive Review of Its Biology, and Its Role as a Potential Target for Anti-Cancer Agents.Frontiers in oncology · 2021Review
- MYC dysfunction modulates stemness and tumorigenesis in breast cancer.International journal of biological sciences · 2021Article
- The Molecular 'Myc-anisms' Behind Myc-Driven Tumorigenesis and the Relevant Myc-Directed Therapeutics.International journal of molecular sciences · 2020Review
- Exploitable metabolic dependencies in MLL-ENL-induced leukemia.Blood advances · 2020Article
- P-TEFb as A Promising Therapeutic Target.Molecules (Basel, Switzerland) · 2020Review
- The mechanism of MYB transcriptional regulation by MLL-AF9 oncoprotein.Scientific reports · 2019Article
- Mission Possible: Advances in MYC Therapeutic Targeting in Cancer.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2019Review
- CDKI-73: an orally bioavailable and highly efficacious CDK9 inhibitor against acute myeloid leukemia.Investigational new drugs · 2019Article
- The CUL5 ubiquitin ligase complex mediates resistance to CDK9 and MCL1 inhibitors in lung cancer cells.eLife · 2019Article
- Recent Treatment Advances and the Role of Nanotechnology, Combination Products, and Immunotherapy in Changing the Therapeutic Landscape of Acute Myeloid Leukemia.Pharmaceutical research · 2019Review
- Transcription regulation ofAnnals of translational medicine · 2018Review
- Combined inhibition of CDK and HDAC as a promising therapeutic strategy for both cutaneous and uveal metastatic melanoma.Oncotarget · 2018Article
- Uncovering BRD4 hyperphosphorylation associated with cellular transformation in NUT midline carcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mixed-lineage leukemia fusion proteins activate their target genes predominantly by stimulating transcriptional elongation. A core component necessary for this activity is cyclin-dependent kinase 9. Here we explored the effectiveness of small molecules targeting this enzyme as potential therapeutics. A screen of seven compounds with anti-CDK9 activity applied to a panel of leukemia cell lines identified flavopiridol and the experimental inhibitor PC585 as superior in efficacy with inhibitory concentrations in the submicromolar range. Both substances induced rapid dephosphorylation of the RNA polymerase II C-terminal domain, accompanied by downregulation of CDK9-dependent transcripts for MYC and HOXA9. Global gene expression analysis indicated the induction of a general stress response program, culminating in widespread apoptosis. Importantly, colony-forming activity in leukemia lines and primary patient samples could be completely inhibited under conditions that did not affect native precursors from bone marrow. In vivo application in a mouse transplant model significantly delayed disease with PC585 showing also oral activity. These results suggest CDK9 inhibition as novel treatment option for mixed-lineage leukemia.
Indexed as
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What OpenQuestion holds
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.