ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019
Inhibition of Bcl-2 Synergistically Enhances the Antileukemic Activity of Midostaurin and Gilteritinib in Preclinical Models of FLT3-Mutated Acute Myeloid Leukemia.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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Who cites it
102 citing papers in PubMed, 175 citations in OpenAlex.
- Long-term outcomes of azacitidine, venetoclax, and gilteritinib in newly diagnosed FLT3-mutated AML.Blood advances · 2026Trial
- Azacitidine, Venetoclax, and Gilteritinib in Newly Diagnosed and Relapsed or RefractoryJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Trial
- Venetoclax Combined with Azacitidine and Homoharringtonine in Relapsed/Refractory AML: A Multicenter, Phase 2 Trial.Journal of hematology & oncology · 2023Trial
- Triplet therapy with venetoclax, FLT3 inhibitor and decitabine for FLT3-mutated acute myeloid leukemia.Blood cancer journal · 2021Trial
- Article
- Targeting FLT3 in Acute Myeloid Leukemia: Structural Insights and Key Challenges.ACS bio & med chem Au · 2026Review
- P300/CBP inhibition with inobrodib in combination with gilteritinib and venetoclax targets leukemia stem cells in epigenetic mutant AML.Science advances · 2026Article
- Synergistic targeting of eIF4A-mediated translation initiation and apoptosis in acute myeloid leukemia.Blood neoplasia · 2026Article
- Midostaurin response in AML is shaped by a progenitor-like cell state selectively targeted by SMAC mimetics.NPJ precision oncology · 2026Article
- Inhibition of CDK9 enhances AML cell death induced by combined venetoclax and azacitidine.Molecular oncology · 2026Article
- Olverembatinib (HQP1351): a third-generation tyrosine kinase inhibitor in the treatment of hematologic and solid malignancies-a comprehensive review of clinical outcomes.Discover oncology · 2026Review
- Article
- Apoptosis-targeting BH3 mimetics: transforming treatment for patients with acute myeloid leukaemia.Nature reviews. Clinical oncology · 2025Review
- Targeting the BCL2 Family: Advances and Challenges in BH3 Mimetic-Based Therapies.International journal of molecular sciences · 2025Review
- Current Therapeutic Strategies for FLT3-Mutated Acute Myeloid Leukemia: A Narrative Review.Cureus · 2025Review
- RNA activation ofMolecular therapy. Nucleic acids · 2025Article
- Sitravatinib combined with venetoclax exerts effective synergy to eliminate acute myeloid leukemia cells with FLT3-ITD mutations.Translational oncology · 2025Article
- Current Treatment Strategies for FLT3-Mutated Acute Myeloid Leukemia in Patients not Candidates for Intensive Chemotherapy.Current oncology reports · 2025Review
- Efficacy and prognostic analysis of venetoclax combined with hypomethylating agents for induction therapy in acute myeloid leukemia: a multi-center real-world study on indication-specific stratification, molecular markers, and hematologic toxicities.Cancer cell international · 2025Article
- Unraveling Venetoclax Resistance: Navigating the Future of HMA/Venetoclax-Refractory AML in the Molecular Era.Cancers · 2025Review
42 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeTo investigate the efficacy of the combination of the FLT3 inhibitors midostaurin or gilteritinib with the Bcl-2 inhibitor venetoclax in FLT3-internal tandem duplication (ITD) acute myeloid leukemia (AML) and the underlying molecular mechanism. EXPERIMENTAL
designUsing both FLT3-ITD cell lines and primary patient samples, Annexin V-FITC/propidium iodide staining and flow cytometry analysis were used to quantify cell death induced by midostaurin or gilteritinib, alone or in combination with venetoclax. Western blot analysis was performed to assess changes in protein expression levels of members of the JAK/STAT, MAPK/ERK, and PI3K/AKT pathways, and members of the Bcl-2 family of proteins. The MV4-11-derived xenograft mouse model was used to assess
resultsThe combination of midostaurin or gilteritinib with venetoclax potently and synergistically induces apoptosis in FLT3-ITD AML cell lines and primary patient samples. The FLT3 inhibitors induced downregulation of Mcl-1, enhancing venetoclax activity. Phosphorylated-ERK expression is induced by venetoclax but abolished by the combination of venetoclax with midostaurin or gilteritinib. Simultaneous downregulation of Mcl-1 by midostaurin or gilteritinib and inhibition of Bcl-2 by venetoclax results in "free" Bim, leading to synergistic induction of apoptosis.
conclusionsInhibition of Bcl-2 via venetoclax synergistically enhances the efficacy of midostaurin and gilteritinib in FLT3-mutated AML.
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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.