ArticleJournal of hematology & oncology2017
Hh/Gli antagonist in acute myeloid leukemia with CBFA2T3-GLIS2 fusion gene.
Article in Journal of hematology & oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- A New Paradigm for Pediatric AML: Improving the Pipeline for Treatments Targeting Cytogenetic and Molecular Alterations.Cancers · 2026Review
- [Acute megakaryoblastic leukemia with CBFA2T3::GLIS2 fusion gene: 3 cases report and literature review].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2026Review
- Transcriptional rewiring by enhancer methylation in CBFA2T3-GLIS2-driven pediatric acute megakaryoblastic leukemia.Genes & diseases · 2026Article
- A Novel Approach to Prognostic Factors and Risk Stratification in Pediatric AML: Case Report and Literature Review.International journal of molecular sciences · 2025Review
- Novel perceptions and insights into the rare hematologic malignancy of acute megakaryocytic leukemia: a multicenter clinical retrospective study.Frontiers in medicine · 2025Article
- Clinical Analysis of Pediatric Acute Megakaryocytic Leukemia With CBFA2T3-GLIS2 Fusion Gene.Journal of pediatric hematology/oncology · 2024Article
- Understanding the Roles of the Hedgehog Signaling Pathway during T-Cell Lymphopoiesis and in T-Cell Acute Lymphoblastic Leukemia (T-ALL).International journal of molecular sciences · 2023Review
- Advances in molecular characterization of pediatric acute megakaryoblastic leukemia not associated with Down syndrome; impact on therapy development.Frontiers in cell and developmental biology · 2023Review
- Acute myeloid leukemia with RAM immunophenotype presenting with extensive mesenteric and retroperitoneal lymphadenopathy: A case report and review of the literature.Leukemia research reports · 2022Article
- CD56, HLA-DR, and CD45 recognize a subtype of childhood AML harboring CBFA2T3-GLIS2 fusion transcript.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2021Article
- Exploiting Clonal Evolution to Improve the Diagnosis and Treatment Efficacy Prediction in Pediatric AML.Cancers · 2021Review
- Galectin-1 promotes vasculogenic mimicry in gastric adenocarcinoma via the Hedgehog/GLI signaling pathway.Aging · 2020Article
- Insights on the Interplay between Cells Metabolism and Signaling: A Therapeutic Perspective in Pediatric Acute Leukemias.International journal of molecular sciences · 2020Review
- A Gli inhibitor GANT61 suppresses cell proliferation, promotes cell apoptosis and induces G1/G0 cycle retardation with a dose- and time-dependent manner through inhibiting Notch pathway in multiple myeloma.Cell cycle (Georgetown, Tex.) · 2020Article
- The genomics of acute myeloid leukemia in children.Cancer metastasis reviews · 2020Review
- Comprehensive Transcriptome Profiling of CrypticClinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Emerging Roles of GLI-Similar Krüppel-like Zinc Finger Transcription Factors in Leukemia and Other Cancers.Trends in cancer · 2019Review
- Review
- CBFA2T3-GLIS2-positive acute myeloid leukaemia. A peculiar paediatric entity.British journal of haematology · 2019Review
- Pediatric Acute Myeloid Leukemia (AML): From Genes to Models Toward Targeted Therapeutic Intervention.Frontiers in pediatrics · 2019Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCBFA2T3-GLIS2 is a fusion gene found in 17% of non-Down syndrome acute megakaryoblastic leukemia (non-DS AMKL, FAB M7) and in 8% of pediatric cytogenetically normal acute myeloid leukemia (CN-AML, in association with several French-American-British (FAB) subtypes). Children with AML harboring this aberration have a poor outcome, regardless of the FAB subtype. This fusion gene drives a peculiar expression pattern and leads to overexpression of some of Hedgehog-related genes. GLI-similar protein 2 (GLIS2) is closely related to the GLI family, the final effectors of classic Hedgehog pathway. These observations lend compelling support to the application of GLI inhibitors in the treatment of AML with the aberration CBFA2T3-GLIS2. GANT61 is, nowadays, the most potent inhibitor of GLI family proteins.
methodsWe exposed to GANT61 AML cell lines and primary cells positive and negative for CBFA2T3-GLIS2 and analyzed the effect on cellular viability, induction of apoptosis, cell cycle, and expression profile.
resultsAs compared to AML cells without GLIS2 fusion, GANT61 exposure resulted in higher sensitivity of both cell lines and primary AML cells carrying CBFA2T3-GLIS2 to undergo apoptosis and G1 cell cycle arrest. Remarkably, gene expression studies demonstrated downregulation of GLIS2-specific signature genes in both treated cell lines and primary cells, in comparison with untreated cells. Moreover, chromatin immunoprecipitation analysis revealed direct regulation by GLIS2 chimeric protein of DNMT1 and DNMT3B, two genes implicated in important epigenetic functions.
conclusionsOur findings indicate that the GLI inhibitor GANT61 may be used to specifically target the CBFA2T3-GLIS2 fusion gene in pediatric AML.
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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.