Trial reportHaematologica2019
Hematopoietic niche drives FLT3-ITD acute myeloid leukemia resistance to quizartinib
Trial report in Haematologica, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
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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.
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Who cites it
54 citing papers in PubMed, 86 citations in OpenAlex.
- Bemcentinib as monotherapy and in combination with low-dose cytarabine in acute myeloid leukemia patients unfit for intensive chemotherapy: a phase 1b/2a trial.Nature communications · 2025Trial
- The type I FLT3 inhibitor XL999 overrides secondary FLT3-ITD mutations that arise under gilteritinib and quizartinib treatment in acute myeloid leukemia.Molecular biomedicine · 2026Article
- Preclinical evaluation of CPL423: a novel potent small-molecule inhibitor of TAM family and FLT3 kinase for cancer therapy.Frontiers in pharmacology · 2026Article
- Article
- Antipsychotic Chlorpromazine Suppresses STAT5 Signaling, Overcomes Resistance Mediated by the Gatekeeper Mutation FLT3-ITD/F691L, and Synergizes with Quizartinib in FLT3-ITD-Positive Cells.Current issues in molecular biology · 2025Article
- Targeting rapid TKI-induced AXL upregulation overcomes adaptive ERK reactivation and exerts antileukemic effects in FLT3/ITD acute myeloid leukemia.Molecular oncology · 2025Article
- Advances and Challenges in Quizartinib-Based FLT3 Inhibition for Acute Myeloid Leukemia: Mechanisms of Resistance and Prospective Combination Therapies.European journal of haematology · 2025Review
- The AXL inhibitor bemcentinib overcomes microenvironment-mediated resistance to pioglitazone in acute myeloid leukemia.The FEBS journal · 2025Article
- Cytokine-mediated CAR T therapy resistance in AML.Nature medicine · 2024Article
- AXL as immune regulator and therapeutic target in Acute Myeloid Leukemia: from current progress to novel strategies.Experimental hematology & oncology · 2024Review
- Ningetinib, a novel FLT3 inhibitor, overcomes secondary drug resistance in acute myeloid leukemia.Cell communication and signaling : CCS · 2024Article
- TP-0184 inhibits FLT3/ACVR1 to overcome FLT3 inhibitor resistance and hinder AML growth synergistically with venetoclax.Leukemia · 2024Article
- Review
- A Receptor Tyrosine Kinase Inhibitor Sensitivity Prediction Model Identifies AXL Dependency in Leukemia.International journal of molecular sciences · 2023Article
- Sitravatinib as a potent FLT3 inhibitor can overcome gilteritinib resistance in acute myeloid leukemia.Biomarker research · 2023Article
- The Translational Landscape Revealed the Sequential Treatment Containing ATRA plus PI3K/AKT Inhibitors as an Efficient Strategy for AML Therapy.Pharmaceutics · 2022Article
- Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective.Signal transduction and targeted therapy · 2022Review
- BMX kinase mediates gilteritinib resistance in FLT3-mutated AML through microenvironmental factors.Blood advances · 2022Article
- Overcoming Resistance: FLT3 Inhibitors Past, Present, Future and the Challenge of Cure.Cancers · 2022Review
- FLT3-inhibitor therapy for prevention and treatment of relapse after allogeneic hematopoietic cell transplantation.International journal of hematology · 2022Review
Corrections and comments
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Authors and funding
22 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Internal tandem duplication in Fms-like tyrosine kinase 3 (FLT3-ITD) is the most frequent mutation observed in acute myeloid leukemia (AML) and correlates with poor prognosis. FLT3 tyrosine kinase inhibitors are promising for targeted therapy. Here, we investigated mechanisms dampening the response to the FLT3 inhibitor quizartinib, which is specific to the hematopoietic niche. Using AML primary samples and cell lines, we demonstrate that convergent signals from the hematopoietic microenvironment drive FLT3-ITD cell resistance to quizartinib through the expression and activation of the tyrosine kinase receptor AXL. Indeed, cytokines sustained phosphorylation of the transcription factor STAT5 in quizartinib-treated cells, which enhanced AXL expression by direct binding of a conserved motif in its genomic sequence. Likewise, hypoxia, another well-known hematopoietic niche hallmark, also enhanced AXL expression. Finally, in a xenograft mouse model, inhibition of AXL significantly increased the response of FLT3-ITD cells to quizartinib exclusively within a bone marrow environment. These data highlight a new bypass mechanism specific to the hematopoietic niche that hampers the response to quizartinib through combined upregulation of AXL activity. Targeting this signaling offers the prospect of a new therapy to eradicate resistant FLT3-ITD leukemic cells hidden within their specific microenvironment, thereby preventing relapses from FLT3-ITD clones.
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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.