ArticleThe Journal of clinical investigation2013
CDX2-driven leukemogenesis involves KLF4 repression and deregulated PPARγ signaling.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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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.
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Who cites it
40 citing papers in PubMed, 54 citations in OpenAlex.
- Phase 1 study of APTO-253 HCl, an inducer of KLF4, in patients with advanced or metastatic solid tumors.Investigational new drugs · 2015Trial
- KLF4/MLL3 complex axis drives NRBP2 transcription to eliminate acute myeloid leukemia cells.Leukemia · 2026Article
- Regulatory Role of Zinc in Acute Promyelocytic Leukemia: Cellular and Molecular Aspects with Therapeutic Implications.International journal of molecular sciences · 2025Review
- NUP214 in Acute Myeloid Leukemia.Cells · 2025Review
- Parbendazole as a promising drug for inducing differentiation of acute myeloid leukemia cells with various subtypes.Communications biology · 2024Article
- Aberrant stem cell and developmental programs in pediatric leukemia.Frontiers in cell and developmental biology · 2024Review
- KLF4 is an epigenetically modulated, context-dependent tumor suppressor.Frontiers in cell and developmental biology · 2024Review
- Krüppel-like Factor 4 Supports the Expansion of Leukemia Stem Cells in MLL-AF9-driven Acute Myeloid Leukemia.Stem cells (Dayton, Ohio) · 2022Article
- In vivo temporal resolution of acute promyelocytic leukemia progression reveals a role ofGenes & development · 2022Article
- Krüppel-like factor 4 promotes survival and expansion in acute myeloid leukemia cells.Oncotarget · 2021Article
- Comprehensive Analysis of E3 Ubiquitin Ligases Reveals Ring Finger Protein 223 as a Novel Oncogene Activated by KLF4 in Pancreatic Cancer.Frontiers in cell and developmental biology · 2021Article
- Somatic Mutations Drive Specific, but Reversible, Epigenetic Heterogeneity States in AML.Cancer discovery · 2020Article
- Pivotal role of DPYSL2A in KLF4-mediated monocytic differentiation of acute myeloid leukemia cells.Scientific reports · 2020Article
- Hematopoietic stem and progenitor cell-restricted Cdx2 expression induces transformation to myelodysplasia and acute leukemia.Nature communications · 2020Article
- Expression of human Krüppel-like factor 3 in peripheral blood as a promising biomarker for acute leukemia.Cancer medicine · 2020Article
- The leukaemia stem cell: similarities, differences and clinical prospects in CML and AML.Nature reviews. Cancer · 2020Review
- Inducible transgene expression in PDX models in vivo identifies KLF4 as a therapeutic target for B-ALL.Biomarker research · 2020Article
- Article
- Concise Review: Regulation of Self-Renewal in Normal and Malignant Hematopoietic Stem Cells by Krüppel-Like Factor 4.Stem cells translational medicine · 2019Review
- The H2A.Z histone variant integrates Wnt signaling in intestinal epithelial homeostasis.Nature communications · 2019Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
Aberrant expression of the homeodomain transcription factor CDX2 occurs in most cases of acute myeloid leukemia (AML) and promotes leukemogenesis, making CDX2, in principle, an attractive therapeutic target. Conversely, CDX2 acts as a tumor suppressor in colonic epithelium. The effectors mediating the leukemogenic activity of CDX2 and the mechanism underlying its context-dependent properties are poorly characterized, and strategies for interfering with CDX2 function in AML remain elusive. We report data implicating repression of the transcription factor KLF4 as important for the oncogenic activity of CDX2, and demonstrate that CDX2 differentially regulates KLF4 in AML versus colon cancer cells through a mechanism that involves tissue-specific patterns of promoter binding and epigenetic modifications. Furthermore, we identified deregulation of the PPARγ signaling pathway as a feature of CDX2-associated AML and observed that PPARγ agonists derepressed KLF4 and were preferentially toxic to CDX2+ leukemic cells. These data delineate transcriptional programs associated with CDX2 expression in hematopoietic cells, provide insight into the antagonistic duality of CDX2 function in AML versus colon cancer, and suggest reactivation of KLF4 expression, through modulation of PPARγ signaling, as a therapeutic modality in a large proportion of AML patients.
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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.