ArticleLeukemia2017
Inactivation of KLF4 promotes T-cell acute lymphoblastic leukemia and activates the MAP2K7 pathway.
Article in Leukemia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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The trial behind it
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Who cites it
35 citing papers in PubMed, 44 citations in OpenAlex.
- KLF4/MLL3 complex axis drives NRBP2 transcription to eliminate acute myeloid leukemia cells.Leukemia · 2026Article
- Off-Target MAP2K7 Inhibition Drives the Antileukemic Activity of the PD-1/PD-L1 inhibitor ACS-69 in Pediatric T-ALL.Research square · 2026Article
- Targeting the JNK Gatekeepers: Structural Evolution and Medicinal Chemistry of MKK4 and MKK7 Inhibitors.Molecules (Basel, Switzerland) · 2026Review
- 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
- Induction of T-Cell Differentiation by KLF4 in T-Cell Acute Lymphoblastic Leukemia Cells Harboring Activating Mutation in NOTCH3.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Identification of common hub genes and construction of immune regulatory networks in aplastic anemia, myelodysplastic syndromes, and acute myeloid leukemia.Frontiers in immunology · 2025Article
- The reprogramming factor KLF4 in normal and malignant blood cells.Frontiers in immunology · 2025Review
- KLF4: a multifunctional nexus connecting tumor progression and immune regulation.Frontiers in immunology · 2025Review
- Epigenetic alterations affecting hematopoietic regulatory networks as drivers of mixed myeloid/lymphoid leukemia.Nature communications · 2024Article
- Suppression of super-enhancer-driven TAL1 expression by KLF4 in T-cell acute lymphoblastic leukemia.Oncogene · 2024Article
- Pharmacological inhibition of the MAP2K7 kinase in human disease.Frontiers in oncology · 2024Review
- KLF4 is an epigenetically modulated, context-dependent tumor suppressor.Frontiers in cell and developmental biology · 2024Review
- Emerging roles of activating transcription factor 2 in the development of breast cancer: a comprehensive review.Precision clinical medicine · 2023Review
- Rational Design of Highly Potent and Selective Covalent MAP2K7 Inhibitors.ACS medicinal chemistry letters · 2023Article
- Antileukemic properties of the kinase inhibitor OTSSP167 in T-cell acute lymphoblastic leukemia.Blood advances · 2023Article
- Targeting Leukemia-Initiating Cells and Leukemic Niches: The Next Therapy Station for T-Cell Acute Lymphoblastic Leukemia?Cancers · 2022Review
- Krüppel-like Factor 4 Supports the Expansion of Leukemia Stem Cells in MLL-AF9-driven Acute Myeloid Leukemia.Stem cells (Dayton, Ohio) · 2022Article
- Emerging roles of activating transcription factor (ATF) family members in tumourigenesis and immunity: Implications in cancer immunotherapy.Genes & diseases · 2022Review
- A Signature of NFrontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with a high incidence of relapse in pediatric ALL. Although most T-ALL patients exhibit activating mutations in NOTCH1, the cooperating genetic events required to accelerate the onset of leukemia and worsen disease progression are largely unknown. Here, we show that the gene encoding the transcription factor KLF4 is inactivated by DNA methylation in children with T-ALL. In mice, loss of KLF4 accelerated the development of NOTCH1-induced T-ALL by enhancing the G1-to-S transition in leukemic cells and promoting the expansion of leukemia-initiating cells. Mechanistically, KLF4 represses the gene encoding the kinase MAP2K7. Our results showed that in murine and pediatric T-ALL, loss of KLF4 leads to aberrant activation of MAP2K7 and of the downstream effectors JNK and ATF2. As a proof-of-concept for the development of a targeted therapy, administration of JNK inhibitors reduced the expansion of leukemia cells in cell-based and patient-derived xenograft models. Collectively, these data uncover a novel function for KLF4 in regulating the MAP2K7 pathway in T-ALL cells, which can be targeted to eradicate leukemia-initiating cells in T-ALL 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.