ArticleMolecular cancer2015
Genome-wide analyses identify KLF4 as an important negative regulator in T-cell acute lymphoblastic leukemia through directly inhibiting T-cell associated genes.
Article in Molecular cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- Krüppel-Like Factor 4, a Hub Gate for Cell Crosstalk in Tumor Microenvironment.Cancer medicine · 2026Review
- Regulatory Role of Zinc in Acute Promyelocytic Leukemia: Cellular and Molecular Aspects with Therapeutic Implications.International journal of molecular sciences · 2025Review
- The reprogramming factor KLF4 in normal and malignant blood cells.Frontiers in immunology · 2025Review
- Krüppel-like factor 4 control of immune cell function.Frontiers in immunology · 2025Review
- Epigenetic alterations affecting hematopoietic regulatory networks as drivers of mixed myeloid/lymphoid leukemia.Nature communications · 2024Article
- Ferritin-mediated mitochondrial iron homeostasis is essential for the survival of hematopoietic stem cells and leukemic stem cells.Leukemia · 2024Article
- Suppression of super-enhancer-driven TAL1 expression by KLF4 in T-cell acute lymphoblastic leukemia.Oncogene · 2024Article
- Aptamer sgc8-Modified PAMAM Nanoparticles for Targeted siRNA Delivery to Inhibit BCL11B in T-Cell Acute Lymphoblastic Leukemia.International journal of nanomedicine · 2024Article
- Activation of ALOX12 by a multi-organelle-orienting photosensitizer drives ACSL4-independent cell ferroptosis.Cell death & disease · 2022Article
- Krüppel-like Factor 4 Supports the Expansion of Leukemia Stem Cells in MLL-AF9-driven Acute Myeloid Leukemia.Stem cells (Dayton, Ohio) · 2022Article
- The Chemokine Receptor CCR8 Is a Target of Chimeric Antigen T Cells for Treating T Cell Malignancies.Frontiers in immunology · 2022Article
- NRF2-mediated signaling is a master regulator of transcription factors in bovine granulosa cells under oxidative stress condition.Cell and tissue research · 2021Article
- Targeting chemokines for acute lymphoblastic leukemia therapy.Journal of hematology & oncology · 2021Review
- 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
- Bcl11b/Ctip2 in Skin, Tooth, and Craniofacial System.Frontiers in cell and developmental biology · 2020Review
- RUNX1 inhibits proliferation and induces apoptosis of t(8;21) leukemia cellsHaematologica · 2019Article
- GZD824 suppresses the growth of human B cell precursor acute lymphoblastic leukemia cells by inhibiting the SRC kinase and PI3K/AKT pathways.Oncotarget · 2017Article
- Systems biology analysis of longitudinal functional response of endothelial cells to shear stress.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Novel tumor-suppressor function of KLF4 in pediatric T-cell acute lymphoblastic leukemia.Experimental hematology · 2017Review
Corrections and comments
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Authors and funding
23 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundKruppel-like factor 4 (KLF4) induces tumorigenesis or suppresses tumor growth in a tissue-dependent manner. However, the roles of KLF4 in hematological malignancies and the mechanisms of action are not fully understood.
methodsInducible KLF4-overexpression Jurkat cell line combined with mouse models bearing cell-derived xenografts and primary T-cell acute lymphoblastic leukemia (T-ALL) cells from four patients were used to assess the functional role of KLF4 in T-ALL cells in vitro and in vivo. A genome-wide RNA-seq analysis was conducted to identify genes regulated by KLF4 in T-ALL cells. Chromatin immunoprecipitation (ChIP) PCR was used to determine direct binding sites of KLF4 in T-ALL cells.
resultsHere we reveal that KLF4 induced apoptosis through the BCL2/BCLXL pathway in human T-ALL cell lines and primary T-ALL specimens. In consistence, mice engrafted with KLF4-overexpressing T-ALL cells exhibited prolonged survival. Interestingly, the KLF4-induced apoptosis in T-ALL cells was compromised in xenografts but the invasion capacity of KLF4-expressing T-ALL cells to hosts was dramatically dampened. We found that KLF4 overexpression inhibited T cell-associated genes including NOTCH1, BCL11B, GATA3, and TCF7. Further mechanistic studies revealed that KLF4 directly bound to the promoters of NOTCH1, BCL2, and CXCR4 and suppressed their expression. Additionally, KLF4 induced SUMOylation and degradation of BCL11B.
conclusionsThese results suggest that KLF4 as a major transcription factor that suppresses the expression of T-cell associated genes, thus inhibiting T-ALL progression.
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