Trial reportNature communications2019
Clinical resistance to crenolanib in acute myeloid leukemia due to diverse molecular mechanisms.
Trial report in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
105 citing papers in PubMed, 1 synthesis or guideline pooled it, 148 citations in OpenAlex.
- FLT3 Tyrosine Kinase Inhibitors for the Treatment of Fit and Unfit Patients with FLT3-Mutated AML: A Systematic Review.International journal of molecular sciences · 2021Pooled it
- Quizartinib and omacetaxine mepesuccinate combination therapy in FLT3-ITD AML: a phase II trial.Nature communications · 2026Trial
- Preclinical Development of Tuspetinib for the Treatment of Acute Myeloid Leukemia.Cancer research communications · 2025Trial
- Imetelstat-mediated alterations in fatty acid metabolism to induce ferroptosis as a therapeutic strategy for acute myeloid leukemia.Nature cancer · 2024Trial
- Molecular profile of FLT3-mutated relapsed/refractory patients with AML in the phase 3 ADMIRAL study of gilteritinib.Blood advances · 2022Trial
- Clonal evolution of acute myeloid leukemia with FLT3-ITD mutation under treatment with midostaurin.Blood · 2021Trial
- A phase 1/2 study of the oral FLT3 inhibitor pexidartinib in relapsed/refractory FLT3-ITD-mutant acute myeloid leukemia.Blood advances · 2020Trial
- XY0206 targets FLT3-dependent resistance states in acute myeloid leukemia.The Journal of clinical investigation · 2026Article
- Targeting oncogenic FLT3 uncovers a ferroptosis vulnerability through selenocysteine recoding in acute myeloid leukaemia.Nature cell biology · 2026Article
- Sphingosine-1-phosphate receptor modulators resensitize FLT3-ITD acute myeloid leukemia cells with NRAS mutations to FLT3 inhibitors.Leukemia · 2026Article
- 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
- Novel treatment strategies in acute myeloid leukemia.Blood research · 2026Review
- Resistance to Targeted Therapy in AML: Current Challenges and Emerging Treatment Strategies.Journal of clinical medicine · 2026Review
- Computer-aided drug design in acute myeloid leukemia: a comprehensive review of advances, challenges, and future prospect.Journal of computer-aided molecular design · 2026Review
- Disruption of gastrointestinal PDGFRαAmerican journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Article
- Prognostic heterogeneity in ASXL1-mutated AML and refinement by an immunophenotype-based score.Frontiers in oncology · 2026Article
- FLT3: A 35-Year Voyage from Discovery to the Next Generation of Targeted Therapy in AML.Cancers · 2025Review
- Novel molecular mechanisms of FLT3 deregulation: from the acute myeloid leukemia experience to therapeutic insights in acute lymphoblastic leukemia.Molecular cancer · 2025Review
- Current Therapeutic Strategies for FLT3-Mutated Acute Myeloid Leukemia: A Narrative Review.Cureus · 2025Review
45 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
30 authors at 6 institutions in 1 country.
Funding
Abstract
FLT3 mutations are prevalent in AML patients and confer poor prognosis. Crenolanib, a potent type I pan-FLT3 inhibitor, is effective against both internal tandem duplications and resistance-conferring tyrosine kinase domain mutations. While crenolanib monotherapy has demonstrated clinical benefit in heavily pretreated relapsed/refractory AML patients, responses are transient and relapse eventually occurs. Here, to investigate the mechanisms of crenolanib resistance, we perform whole exome sequencing of AML patient samples before and after crenolanib treatment. Unlike other FLT3 inhibitors, crenolanib does not induce FLT3 secondary mutations, and mutations of the FLT3 gatekeeper residue are infrequent. Instead, mutations of NRAS and IDH2 arise, mostly as FLT3-independent subclones, while TET2 and IDH1 predominantly co-occur with FLT3-mutant clones and are enriched in crenolanib poor-responders. The remaining patients exhibit post-crenolanib expansion of mutations associated with epigenetic regulators, transcription factors, and cohesion factors, suggesting diverse genetic/epigenetic mechanisms of crenolanib resistance. Drug combinations in experimental models restore crenolanib sensitivity.
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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.