ArticleBlood2019
A KLF4-DYRK2-mediated pathway regulating self-renewal in CML stem cells.
Article in Blood, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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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.
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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
29 citing papers in PubMed, 44 citations in OpenAlex.
- The dual fate of DYRK2 in cancer: balancing the light and dark side of tumorigenesis.Cancer metastasis reviews · 2026Review
- Epigenetic mechanisms controlling human leukemia stem cells and therapy resistance.Nature communications · 2025Article
- Acute myeloid leukemia drug resistance: targetable nodes and the clinical trajectory of small-molecule inhibitors.Frontiers in pharmacology · 2025Review
- The reprogramming factor KLF4 in normal and malignant blood cells.Frontiers in immunology · 2025Review
- The diverse functions of DYRK2 in response to cellular stress.Histology and histopathology · 2024Review
- Exploiting the potential of the ubiquitin-proteasome system in overcoming tyrosine kinase inhibitor resistance in chronic myeloid leukemia.Genes & diseases · 2024Review
- Functional Roles of DYRK2 as a Tumor Regulator.Current issues in molecular biology · 2023Review
- Article
- KLF4 transcription factor in tumorigenesis.Cell death discovery · 2023Review
- Krüppel-like factors in tumors: Key regulators and therapeutic avenues.Frontiers in oncology · 2023Review
- Krüppel-like Factor 4 Supports the Expansion of Leukemia Stem Cells in MLL-AF9-driven Acute Myeloid Leukemia.Stem cells (Dayton, Ohio) · 2022Article
- Mitochondrial oxidative phosphorylation is dispensable for survival of CD34Cell death & disease · 2022Article
- In vivo temporal resolution of acute promyelocytic leukemia progression reveals a role ofGenes & development · 2022Article
- The Impact of Iron Chelators on the Biology of Cancer Stem Cells.International journal of molecular sciences · 2021Review
- Chronic myeloid leukemia stem cells: targeting therapeutic implications.Stem cell research & therapy · 2021Review
- Targeting Leukemic Stem Cells in Chronic Myeloid Leukemia: Is It Worth the Effort?International journal of molecular sciences · 2021Review
- Dual-Specificity, Tyrosine Phosphorylation-Regulated Kinases (DYRKs) and cdc2-Like Kinases (CLKs) in Human Disease, an Overview.International journal of molecular sciences · 2021Review
- Current Methods of Post-Translational Modification Analysis and Their Applications in Blood Cancers.Cancers · 2021Review
- Krüppel-like factor 4 promotes survival and expansion in acute myeloid leukemia cells.Oncotarget · 2021Article
- Review
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Leukemia stem cells are a rare population with a primitive progenitor phenotype that can initiate, sustain, and recapitulate leukemia through a poorly understood mechanism of self-renewal. Here, we report that Krüppel-like factor 4 (KLF4) promotes disease progression in a murine model of chronic myeloid leukemia (CML)-like myeloproliferative neoplasia by repressing an inhibitory mechanism of preservation in leukemia stem/progenitor cells with leukemia-initiating capacity. Deletion of the Klf4 gene severely abrogated the maintenance of BCR-ABL1(p210)-induced CML by impairing survival and self-renewal in BCR-ABL1+ CD150+ lineage-negative Sca-1+ c-Kit+ leukemic cells. Mechanistically, KLF4 repressed the Dyrk2 gene in leukemic stem/progenitor cells; thus, loss of KLF4 resulted in elevated levels of dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 2 (DYRK2), which were associated with inhibition of survival and self-renewal via depletion of c-Myc protein and p53 activation. In addition to transcriptional regulation, stabilization of DYRK2 protein by inhibiting ubiquitin E3 ligase SIAH2 with vitamin K3 promoted apoptosis and abrogated self-renewal in murine and human CML stem/progenitor cells. Altogether, our results suggest that DYRK2 is a molecular checkpoint controlling p53- and c-Myc-mediated regulation of survival and self-renewal in CML cells with leukemic-initiating capacity that can be targeted with small molecules.
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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.