ArticleLeukemia2013
Mutations of FLT3/ITD confer resistance to multiple tyrosine kinase inhibitors.
Article in Leukemia, 2013. 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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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
68 citing papers in PubMed, 113 citations in OpenAlex.
- XY0206 targets FLT3-dependent resistance states in acute myeloid leukemia.The Journal of clinical investigation · 2026Trial
- Crenolanib is a potent inhibitor of FLT3 with activity against resistance-conferring point mutants.Blood · 2014Trial
- XY0206: A promising sunitinib-derived FLT3 inhibitor targeting therapy-resistant acute myeloid leukemia.The Journal of clinical investigation · 2026Article
- Review
- SGI-7079 as a novel type I FLT3 inhibitor overcomes resistance to gilteritinib and quizartinib mediated by ITD and TKD mutations in acute myeloid leukemia.NPJ precision oncology · 2026Article
- Review
- Article
- Ningetinib, a novel FLT3 inhibitor, overcomes secondary drug resistance in acute myeloid leukemia.Cell communication and signaling : CCS · 2024Article
- Characterisation of FLT3 alterations in childhood acute lymphoblastic leukaemia.British journal of cancer · 2024Article
- GNF-7, a novel FLT3 inhibitor, overcomes drug resistance for the treatment of FLT3‑ITD acute myeloid leukemia.Cancer cell international · 2023Article
- Blockade of de novo pyrimidine biosynthesis triggers autophagic degradation of oncoprotein FLT3-ITD in acute myeloid leukemia.Oncogene · 2023Article
- AML under the Scope: Current Strategies and Treatment Involving FLT3 Inhibitors and Venetoclax-Based Regimens.International journal of molecular sciences · 2023Review
- Review
- An overview of arsenic trioxide-involved combined treatment algorithms for leukemia: basic concepts and clinical implications.Cell death discovery · 2023Review
- How ITD Insertion Sites Orchestrate the Biology and Disease of FLT3-ITD-Mutated Acute Myeloid Leukemia.Cancers · 2023Review
- DNA damage accumulation and repair defects in FLT3-ITD acute myeloid leukemia: Implications for clonal evolution and disease progression.Hematological oncology · 2023Review
- Safety profile of vascular endothelial growth factor receptor tyrosine-kinase inhibitors in pediatrics: a pharmacovigilance disproportionality analysis.Frontiers in pharmacology · 2023Article
- Overcoming Resistance: FLT3 Inhibitors Past, Present, Future and the Challenge of Cure.Cancers · 2022Review
- Discovery of imidazo[1,2-a]pyridine-thiophene derivatives as FLT3 and FLT3 mutants inhibitors for acute myeloid leukemia through structure-based optimization of an NEK2 inhibitor.European journal of medicinal chemistry · 2021Article
- Networking for advanced molecular diagnosis in acute myeloid leukemia patients is possible: the PETHEMA NGS-AML projectHaematologica · 2021Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
FMS-like tyrosine kinase 3 (FLT3) normally functions in the survival/proliferation of hematopoietic stem/progenitor cells, but its constitutive activation by internal tandem duplication (ITD) mutations correlates with a poor prognosis in AML. The development of FLT3 tyrosine kinase inhibitors (TKI) is a promising strategy, but resistance that arises during the course of treatment caused by secondary mutations within the mutated gene itself poses a significant challenge. In an effort to predict FLT3 resistance mutations that might develop in patients, we used saturation mutagenesis of FLT3/ITD followed by selection of transfected cells in FLT3 TKI. We identified F621L, A627P, F691L and Y842C mutations in FLT3/ITD that confer varying levels of resistance to FLT3 TKI. Western blotting confirmed that some FLT3 TKI were ineffective at inhibiting FLT3 autophosphorylation and signaling through MAP kinase, STAT5 and AKT in some mutants. Balb/c mice transplanted with the FLT3/ITD Y842C mutation confirmed resistance to sorafenib in vivo but not to lestaurtinib. These results indicate a growing number of FLT3 mutations that are likely to be encountered in patients. Such knowledge, combined with known remaining sensitivity to other FLT3 TKI, will be important to establish as secondary drug treatments that can be substituted when these mutants are encountered.
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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.