ArticleThe Journal of clinical investigation2012
Targeting CDK1 promotes FLT3-activated acute myeloid leukemia differentiation through C/EBPα.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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Who cites it
42 citing papers in PubMed, 61 citations in OpenAlex.
- The prognostic impact of CEBPA mutation in acute myeloid leukemia patients undergoing allogeneic hematopoietic stem cell transplantation.Bone marrow transplantation · 2026Article
- Mesenchymal stem cell-derived extracellular vesicles attenuate liver transplantation-induced ischemia/reperfusion injury by suppressing hepatocellular complement C5 expression.Journal of nanobiotechnology · 2026Article
- CDK1 Signaling in Cancer Treatment: Advances in AI-based Strategies and Tools for New Cancer Drug Discovery.Combinatorial chemistry & high throughput screening · 2026Article
- Kuanxiong aerosol protects against coronary microvascular dysfunction through improving angiogenesis via HIF-1α-ITGAX axis.Frontiers in pharmacology · 2026Article
- Synergistic potential of CDK4/6 inhibitors and ATRA in non-APL AML.British journal of haematology · 2025Article
- WNK1 signalling regulates amino acid transport and mTORC1 activity to sustain acute myeloid leukaemia growth.Nature communications · 2025Article
- BKT300: A Novel Anti-Leukemic Small Molecule Targeting the Protein Regulator of Cytokinesis 1 (PRC1) Pathway.Research square · 2025Article
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- Reverse Phase Proteomic Array Profiling of Asparagine Synthetase Expression in Newly Diagnosed Acute Myeloid Leukemia.Journal of proteome research · 2024Article
- Upregulation of lnc-FOXD2-AS1, CDC45, and CDK1 in patients with primary non-M3 AML is associated with a worse prognosis.Blood research · 2024Article
- Whole blood ratio ofFrontiers in medicine · 2024Article
- Targeting CDK1 in cancer: mechanisms and implications.NPJ precision oncology · 2023Review
- Cytarabine-induced differentiation of AML cells depends on Chk1 activation and shares the mechanism with inhibitors of DHODH and pyrimidine synthesis.Scientific reports · 2022Article
- Article
- Combinatorial molecule screening identified a novel diterpene and the BET inhibitor CPI-203 as differentiation inducers of primary acute myeloid leukemia cells.Haematologica · 2021Article
- DNMT3A Mutation-Induced CDK1 Overexpression Promotes Leukemogenesis by Modulating the Interaction between EZH2 and DNMT3A.Biomolecules · 2021Article
- Differentiation therapy of myeloid leukemia: four decades of development.Haematologica · 2021Review
- CCAAT enhancer binding protein alpha (CEBPA) biallelic acute myeloid leukaemia: cooperating lesions, molecular mechanisms and clinical relevance.British journal of haematology · 2020Review
- Transcriptome Reprogramming of CD11bFrontiers in cell and developmental biology · 2020Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
Mutations that activate the fms-like tyrosine kinase 3 (FLT3) receptor are among the most prevalent mutations in acute myeloid leukemias. The oncogenic role of FLT3 mutants has been attributed to the abnormal activation of several downstream signaling pathways, such as STAT3, STAT5, ERK1/2, and AKT. Here, we discovered that the cyclin-dependent kinase 1 (CDK1) pathway is also affected by internal tandem duplication mutations in FLT3. Moreover, we also identified C/EBPα, a granulopoiesis-promoting transcription factor, as a substrate for CDK1. We further demonstrated that CDK1 phosphorylates C/EBPα on serine 21, which inhibits its differentiation-inducing function. Importantly, we found that inhibition of CDK1 activity relieves the differentiation block in cell lines with mutated FLT3 as well as in primary patient-derived peripheral blood samples. Clinical trials with CDK1 inhibitors are currently under way for various malignancies. Our data strongly suggest that targeting the CDK1 pathway might be applied in the treatment of FLT3ITD mutant leukemias, especially those resistant to FLT3 inhibitor therapies.
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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.