ArticleBlood advances2022
BMX kinase mediates gilteritinib resistance in FLT3-mutated AML through microenvironmental factors.
Article in Blood advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 13 citations in OpenAlex.
- A Phase 1b/2 Study of TP-0903 and Decitabine Targeting Mutant TP53 and/or Complex Karyotype in Patients with Untreated Acute Myeloid Leukemia ≥Age 60 Years.Cancer research communications · 2025Trial
- Targeting the BMX in cancer: molecular mechanisms and emerging therapeutic strategies.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Bone marrow kinase X-linked in pulmonary diseases: pathogenic gene, diagnostic biomarker, and treatment target-a narrative review.Translational pediatrics · 2026Review
- Quizartinib Resistance Mutations and Treatment Outcomes in Relapsed or Refractory FLT3-ITD-Positive AML.Cancer science · 2026Article
- Riding toward Selectivity: Optimization of Covalent 7-Azaindole-Based BMX Kinase Inhibitors.Journal of medicinal chemistry · 2026Article
- Discovery of Dihydropyrimido-Pyrimidine-Based Bone Marrow Tyrosine Kinase Gene in Chromosome X Protein Proteolysis-Targeting Chimeras for the Treatment of Prostate Cancer.ACS medicinal chemistry letters · 2026Article
- Novel molecular mechanisms of FLT3 deregulation: from the acute myeloid leukemia experience to therapeutic insights in acute lymphoblastic leukemia.Molecular cancer · 2025Review
- Drug-Drug Interaction Liabilities with BTK Inhibitor TL-895.Cancer research communications · 2025Article
- Targeting ribonucleotide reductase to enhance the antileukemic activity of gilteritinib against chemoresistantASPET discovery · 2025Article
- RSK1 dependency in FLT3-ITD acute myeloid leukemia.Blood cancer journal · 2024Article
- Pharmacological inhibition of RAS overcomes FLT3 inhibitor resistance in FLT3-ITD+ AML through AP-1 and RUNX1.iScience · 2024Article
- FLT3 tyrosine kinase inhibition modulates PRC2 and promotes differentiation in acute myeloid leukemia.Leukemia · 2024Article
- Therapeutic Targeting of FLT3 in Acute Myeloid Leukemia: Current Status and Novel Approaches.OncoTargets and therapy · 2022Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Despite the clinical benefit associated with gilteritinib in relapsed/refractory acute myeloid leukemia (AML), most patients eventually develop resistance through unknown mechanisms. To delineate the mechanistic basis of resistance to gilteritinib, we performed targeted sequencing and scRNASeq on primary FLT3-ITD-mutated AML samples. Co-occurring mutations in RAS pathway genes were the most common genetic abnormalities, and unresponsiveness to gilteritinib was associated with increased expression of bone marrow-derived hematopoietic cytokines and chemokines. In particular, we found elevated expression of the TEK-family kinase, BMX, in gilteritinib-unresponsive patients pre- and post-treatment. BMX contributed to gilteritinib resistance in FLT3-mutant cell lines in a hypoxia-dependent manner by promoting pSTAT5 signaling, and these phenotypes could be reversed with pharmacological inhibition and genetic knockout. We also observed that inhibition of BMX in primary FLT3-mutated AML samples decreased chemokine secretion and enhanced the activity of gilteritinib. Collectively, these findings indicate a crucial role for microenvironment-mediated factors modulated by BMX in the escape from targeted therapy and have implications for the development of novel therapeutic interventions to restore sensitivity to gilteritinib.
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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.