ArticleOncotarget2017
FLT3 activating mutations display differential sensitivity to multiple tyrosine kinase inhibitors.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- Review
- TIP-20, a novel feline McDonough sarcoma-like tyrosine kinase 3 inhibitor with potent antileukemia activity.The Journal of international medical research · 2026Article
- Novel molecular mechanisms of FLT3 deregulation: from the acute myeloid leukemia experience to therapeutic insights in acute lymphoblastic leukemia.Molecular cancer · 2025Review
- Assessment of chromatin remodeling of acute myeloid leukemia cells treated with gilteritinib: a case report.Journal of medical case reports · 2025Article
- FLT3 targeting in the modern era: from clonal selection to combination therapies.International journal of hematology · 2024Review
- Characterisation of FLT3 alterations in childhood acute lymphoblastic leukaemia.British journal of cancer · 2024Article
- Epigenetic activation of the FLT3 gene by ZNF384 fusion confers a therapeutic susceptibility in acute lymphoblastic leukemia.Nature communications · 2022Article
- Overcoming Resistance: FLT3 Inhibitors Past, Present, Future and the Challenge of Cure.Cancers · 2022Review
- Clinical outcomes in patients with relapsed/refractory FLT3-mutated acute myeloid leukemia treated with gilteritinib who received prior midostaurin or sorafenib.Blood cancer journal · 2022Article
- Therapeutic Management of Patients with FLT3 + Acute Myeloid Leukemia: Case Reports and Focus on Gilteritinib Monotherapy.Pharmacogenomics and personalized medicine · 2022Article
- A method for overcoming plasma protein inhibition of tyrosine kinase inhibitors.Blood cancer discovery · 2021Article
- FLT3 tyrosine kinase inhibitors synergize with BCL-2 inhibition to eliminate FLT3/ITD acute leukemia cells through BIM activation.Signal transduction and targeted therapy · 2021Article
- Deletions in FLT-3 juxtamembrane domain define a new class of pathogenic mutations: case report and systematic analysis.Blood advances · 2021Article
- Antileukemic efficacy of a potent artemisinin combined with sorafenib and venetoclax.Blood advances · 2021Article
- A Novel 2-Carbon-Linked Dimeric Artemisinin With Potent Antileukemic Activity and Favorable Pharmacology.Frontiers in oncology · 2021Article
- Novel Approaches to Target Mutant FLT3 Leukaemia.Cancers · 2020Review
- Review
- Genomic markers of midostaurin drug sensitivity in FLT3 mutated and FLT3 wild-type acute myeloid leukemia patients.Oncotarget · 2020Article
- Proteolysis-targeting chimera (PROTAC) for targeted protein degradation and cancer therapy.Journal of hematology & oncology · 2020Review
- Theoretical Studies Aimed at Finding FLT3 Inhibitors and a Promising Compound and Molecular Pattern with Dual Aurora B/FLT3 Activity.Molecules (Basel, Switzerland) · 2020Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Fms-like tyrosine kinase-3 (FLT3) is a receptor tyrosine kinase that normally functions in hematopoietic cell survival, proliferation and differentiation. Constitutively activating mutations of FLT3 map predominately to the juxtamembrane domain (internal tandem duplications; ITD) or the activation loop (AL) of the kinase domain and are detected in about 1/3 of de novo acute myeloid leukemia (AML) patients. Small molecule tyrosine kinase inhibitors (TKI) effectively target FLT3/ITD mutations, but some activating mutations, particularly those on the AL, are relatively resistant to many FLT3 TKI. We reproduced many of the AL or other non-ITD activating mutations and tested 13 FLT3 TKI for their activity against these and wild-type FLT3. All 13 TKI tested inhibited BaF3/ITD cell proliferation in a concentration-dependent manner as reported, but most TKI exhibited a wide range of differential activity against AL and other point mutants. Western blotting results examining inhibition of FLT3 autophosphorylation and signaling pathways indicate that many AL mutations reduce TKI binding. Most FLT3 TKI effectively target wild-type FLT3 signaling. As a demonstration of this differential activity, treatment of BaF3 D835Y cells transplanted in BALB/c mice with sorafenib showed no effect in vivo against this mutant whereas lestaurtinib proved effective at reducing disease burden. Thus, while FLT3 TKI have been selected based on their ability to inhibit FLT3/ITD, the selection of appropriate TKI for AML patients with FLT3 AL and other activating point mutations requires personalized consideration.
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