ArticleLeukemia2022
Translatome proteomics identifies autophagy as a resistance mechanism to on-target FLT3 inhibitors in acute myeloid leukemia.
Article in Leukemia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 28 citations in OpenAlex.
- Differential protein expression analysis of quantitative mass spectrometry data using DEqMS.Nature protocols · 2026Review
- Selective targeting of RSK signaling with PMD-026 suppresses FLT3-activated acute myeloid leukemia while sparing normal hematopoiesis.Leukemia · 2026Article
- Article
- TRIM22-mediated ubiquitin-dependent degradation of FLT3-ITD overcomes TKI resistance in acute myeloid leukemia.Life medicine · 2026Article
- Bortezomib synergizes with homoharringtonine in FLT3-ITD-relapsed/refractory acute myeloid leukemia by inducing FLT3-ITD protein degradation.Clinical and experimental medicine · 2026Article
- Autophagy inhibition potentiates the antileukemic effect of FLT3 inhibitors and overcomes resistance in FLT3-ITD acute myeloid leukemia.Cell death discovery · 2026Article
- Mitophagy-driven prognosis in pediatric acute myeloid leukemia: a new frontier.Scientific reports · 2026Article
- Autophagy in Cancer: Context-Dependent Regulation and Precision Nanomedicine-Enabled Therapeutic Targeting.Biomedicines · 2026Review
- Autophagy Inhibition Enhances the Antitumor Efficacy of MET Targeting in MET-High Pancreatic Cancer.Oncology research · 2026Article
- RSK signaling in myeloid malignancies: biology, disease dependency, and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- Targeting cell death pathways in acute myeloid leukemia: Molecular mechanisms and clinical implications (Review).Oncology reports · 2025Review
- Rationally designed BCR-ABL kinase inhibitors for improved leukemia treatment via covalent and pro-/dual-drug targeting strategies.Journal of advanced research · 2025Article
- RNF38 promotes gilteritinib resistance in acute myeloid leukemia via inducing autophagy by regulating ubiquitination of LMX1A.Cell biology and toxicology · 2024Article
- Current Understanding of the Role of Autophagy in the Treatment of Myeloid Leukemia.International journal of molecular sciences · 2024Review
- Machine learning-based biomarker screening for acute myeloid leukemia prognosis and therapy from diverse cell-death patterns.Scientific reports · 2024Article
- Application of omics in the diagnosis, prognosis, and treatment of acute myeloid leukemia.Biomarker research · 2024Review
- Crosstalk between autophagy and metabolism: implications for cell survival in acute myeloid leukemia.Cell death discovery · 2024Review
- Mass Spectrometry-Based Proteogenomics: New Therapeutic Opportunities for Precision Medicine.Annual review of pharmacology and toxicology · 2024Review
- Mapping the proteogenomic landscape enables prediction of drug response in acute myeloid leukemia.Cell reports. Medicine · 2024Article
- Progress in the study of autophagy-related proteins affecting resistance to chemotherapeutic drugs in leukemia.Frontiers in cell and developmental biology · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Internal tandem duplications (ITD) in the receptor tyrosine kinase FLT3 occur in 25 % of acute myeloid leukemia (AML) patients, drive leukemia progression and confer a poor prognosis. Primary resistance to FLT3 kinase inhibitors (FLT3i) quizartinib, crenolanib and gilteritinib is a frequent clinical challenge and occurs in the absence of identifiable genetic causes. This suggests that adaptive cellular mechanisms mediate primary resistance to on-target FLT3i therapy. Here, we systematically investigated acute cellular responses to on-target therapy with multiple FLT3i in FLT3-ITD + AML using recently developed functional translatome proteomics (measuring changes in the nascent proteome) with phosphoproteomics. This pinpointed AKT-mTORC1-ULK1-dependent autophagy as a dominant resistance mechanism to on-target FLT3i therapy. FLT3i induced autophagy in a concentration- and time-dependent manner specifically in FLT3-ITD + cells in vitro and in primary human AML cells ex vivo. Pharmacological or genetic inhibition of autophagy increased the sensitivity to FLT3-targeted therapy in cell lines, patient-derived xenografts and primary AML cells ex vivo. In mice xenografted with FLT3-ITD + AML cells, co-treatment with oral FLT3 and autophagy inhibitors synergistically impaired leukemia progression and extended overall survival. Our findings identify a molecular mechanism responsible for primary FLT3i treatment resistance and demonstrate the pre-clinical efficacy of a rational combination treatment strategy targeting both FLT3 and autophagy induction.
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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.