ArticleOncotarget2016
Co-expression of wild-type FLT3 attenuates the inhibitory effect of FLT3 inhibitor on FLT3 mutated leukemia cells.
Article in Oncotarget, 2016. 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.
- The diagnostic potential of nanobodies in acute myeloid leukemia.Molecular biology reports · 2026Review
- Resistance to Targeted Therapy in AML: Current Challenges and Emerging Treatment Strategies.Journal of clinical medicine · 2026Review
- Review
- Recent progress in AML with recurrent genetic abnormalities.International journal of hematology · 2024Review
- FLT3 targeting in the modern era: from clonal selection to combination therapies.International journal of hematology · 2024Review
- Rational polypharmacological targeting of FLT3, JAK2, ABL, and ERK1 suppresses the adaptive resistance to FLT3 inhibitors in AML.Blood advances · 2023Article
- Targeting FLT3 Mutation in Acute Myeloid Leukemia: Current Strategies and Future Directions.Cancers · 2023Review
- Advances in clinical studies of FLT3 inhibitors in acute myeloid leukemia.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2022Review
- "FLipping" the Story: FLT3-Mutated Acute Myeloid Leukemia and the Evolving Role of FLT3 Inhibitors.Cancers · 2022Review
- Refining AML Treatment: The Role of Genetics in Response and Resistance Evaluation to New Agents.Cancers · 2022Review
- A review of FLT3 inhibitors in acute myeloid leukemia.Blood reviews · 2022Review
- Therapeutic Targeting of FLT3 in Acute Myeloid Leukemia: Current Status and Novel Approaches.OncoTargets and therapy · 2022Review
- Multiplexed single-cell mass cytometry reveals distinct inhibitory effects on intracellular phosphoproteins by midostaurin in combination with chemotherapy in AML cells.Experimental hematology & oncology · 2021Article
- Novel Approaches to Target Mutant FLT3 Leukaemia.Cancers · 2020Review
- Review
- Impact of numerical variation, allele burden, mutation length and co-occurring mutations on the efficacy of tyrosine kinase inhibitors in newly diagnosed FLT3- mutant acute myeloid leukemia.Blood cancer journal · 2020Article
- Overcoming Resistance to FLT3 Inhibitors in the Treatment ofInternational journal of molecular sciences · 2020Review
- FLT3 mutations in acute myeloid leukemia: Therapeutic paradigm beyond inhibitor development.Cancer science · 2020Review
- Targeting Immunophenotypic Markers on Leukemic Stem Cells: How Lessons from Current Approaches and Advances in the Leukemia Stem Cell (LSC) Model Can Inform Better Strategies for Treating Acute Myeloid Leukemia (AML).Cold Spring Harbor perspectives in medicine · 2020Review
- Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
FLT3 mutation is found in about 30% of acute myeloid leukemia (AML) patients and is associated with a poor prognosis. Several FLT3 inhibitors are undergoing investigation, while their clinical efficacies were lower than expected and several resistant mechanisms to FLT3 inhibitors have been demonstrated. Although most AML cells harboring FLT3 mutation co-express wild-type (Wt)-FLT3, it is not fully understood how Wt-FLT3 expression is associated with the resistance to FLT3 inhibitors. In this study, we elucidated a resistant mechanism by which FL-dependent Wt-FLT3 activation reduced inhibitory effects of FLT3 inhibitors. We demonstrated that FL-stimulation much more strongly reduced growth inhibitory effects of FLT3 inhibitors on Wt- and mutant-FLT3 co-expressing cells than sole mutant-FLT3 expressing cells both in vitro and in vivo. It was also confirmed that FL impaired the anti-leukemia effects of FLT3 inhibitors on primary AML cells. We elucidated that FL impeded the inhibitory effects of FLT3 inhibitors mainly through the activation of Wt-FLT3, but not mutated FLT3, in the Wt- and ITD-FLT3 co-expressing cells. Furthermore, FL-induced activation of Wt-FLT3-MAPK axis was the dominant pathway for the resistance, and the glycosylation of Wt-FLT3 was also vital for FL-dependent kinase activation and following resistance to FLT3 inhibitors. Thus, we clarified the importance of co-expressing Wt-FLT3 in resistance to FLT3 inhibitors. These findings provide us with important implications for clinical application and new strategies to improve clinical outcomes of FLT3 inhibitors.
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