ArticleSignal transduction and targeted therapy2021
FLT3 tyrosine kinase inhibitors synergize with BCL-2 inhibition to eliminate FLT3/ITD acute leukemia cells through BIM activation.
Article in Signal transduction and targeted therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 106 citations in OpenAlex.
- Azacitidine, Venetoclax, and Gilteritinib in Newly Diagnosed and Relapsed or RefractoryJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Trial
- HIPK2 exhibits context dependent dualistic effects and combinatorial inhibition of HIPK2-NLK-MAPK11 axis manifests synergism against gastric cancer.Human cell · 2026Article
- Review
- Activation of c-Myc confers resistance to venetoclax via inhibition of Bim in t(8;21)-positive acute myeloid leukemia.Cell communication and signaling : CCS · 2026Article
- An unprecedented potent inhibitor of MV4-11 cells: investigations into the mechanism of action beyond FLT3 inhibition.Bioorganic chemistry · 2026Article
- An emerging triplet option for newly diagnosedHaematologica · 2026Article
- FBXO3-mediated DUSP9 ubiquitination promotes leukemia stem cell maintenance and tyrosine kinase inhibitor resistance in chronic myeloid leukemia.Cell reports. Medicine · 2026Article
- FOXM1 induces therapy resistance and inhibits apoptosis in a variety of human cancers.Cell death & disease · 2026Review
- 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
- Chronic ER Stress Triggers Cell-Surface Chaperones as the Therapeutic Targets of CAR Cells in Acute Myeloid Leukemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Phenazine 5,10-dioxide analogues as potential therapeutics in AML: Efficacy on patient-derived blasts, in zebrafish larvae xenografts and synergy with venetoclax.Translational oncology · 2026Article
- Integrative Bioinformatics Reveals Novel Molecular Mechanisms and Therapeutic Targets in Acute Myeloid Leukaemia.Journal of cellular and molecular medicine · 2026Article
- Article
- Apoptosis-targeting BH3 mimetics: transforming treatment for patients with acute myeloid leukaemia.Nature reviews. Clinical oncology · 2025Review
- Novel molecular mechanisms of FLT3 deregulation: from the acute myeloid leukemia experience to therapeutic insights in acute lymphoblastic leukemia.Molecular cancer · 2025Review
- Targeting the BCL2 Family: Advances and Challenges in BH3 Mimetic-Based Therapies.International journal of molecular sciences · 2025Review
- Genotype-guided comparison of VEN/HMA versus intensive chemotherapy in newly diagnosed intermediate-risk AML: a multicenter real-world study.Blood cancer journal · 2025Article
- Acute myeloid leukemia with plasmacytoid dendritic cell proliferation: A case report and literature review.Oncology letters · 2025Article
- Current Therapeutic Strategies for FLT3-Mutated Acute Myeloid Leukemia: A Narrative Review.Cureus · 2025Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Tyrosine kinase inhibitors (TKIs) targeting FLT3 have shown activity but when used alone have achieved limited success in clinical trials, suggesting the need for combination with other drugs. We investigated the combination of FLT3 TKIs (Gilteritinib or Sorafenib), with Venetoclax, a BCL-2 selective inhibitor (BCL-2i), on FLT3/ITD leukemia cells. The combination of a FLT3 TKI and a BCL-2i synergistically reduced cell proliferation and enhanced apoptosis/cell death in FLT3/ITD cell lines and primary AML samples. Venetoclax also re-sensitized FLT3 TKI-resistant cells to Gilteritinib or Sorafenib treatment, mediated through MAPK pathway inhibition. Gilteritinib treatment alone dissociated BIM from MCL-1 but increased the binding of BIM to BCL-2. Venetoclax treatment enhanced the binding of BIM to MCL-1 but dissociated BIM from BCL-2. Treatment with the drugs together resulted in dissociation of BIM from both BCL-2 and MCL-1, with an increased binding of BIM to the cell death mediator BAX, leading to increased apoptosis. These findings suggest that Venetoclax mitigates the unintended pro-survival effects of FLT3 TKI mainly through the dissociation of BIM and BCL-2 and also decreased BIM expression. This study provides evidence that the addition of BCL-2i enhances the effect of FLT3 TKI therapy in FLT3/ITD AML treatment.
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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.