ArticleLeukemia2018
RET-mediated autophagy suppression as targetable co-dependence in acute myeloid leukemia.
Article in Leukemia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 66 citations in OpenAlex.
- XY0206 targets FLT3-dependent resistance states in acute myeloid leukemia.The Journal of clinical investigation · 2026Article
- 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
- Review
- Autophagy and Lipid Metabolism as a Therapeutic Target for Overcoming Drug Resistance in Acute Myeloid Leukemia.Life (Basel, Switzerland) · 2026Review
- Recent Advances in FLT3-Based Dual Inhibitors: A Promising Strategy for the Treatment of Acute Myeloid Leukemia.Current medicinal chemistry · 2026Review
- The multiplex crosstalk between non-coding RNAs, programmed cell death and related mechanisms: a dynamic duo in hematological malignancies.Cancer cell international · 2025Review
- Multi-context modeling of driver pathways reveals common and specific mechanisms across 23 cancer types.PLoS computational biology · 2025Article
- Interplay between LncRNAs and autophagy-related pathways in leukemia: mechanisms and clinical implications.Medical oncology (Northwood, London, England) · 2025Review
- Current Understanding of the Role of Autophagy in the Treatment of Myeloid Leukemia.International journal of molecular sciences · 2024Review
- Article
- Enhancer-activated RET confers protection against oxidative stress to KMT2A-rearranged acute myeloid leukemia.Cancer science · 2024Article
- Review
- Targeting regulated cell death pathways in acute myeloid leukemia.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Article
- Potential role of autophagy induced by FLT3-ITD and acid ceramidase in acute myeloid leukemia chemo-resistance: new insights.Cell communication and signaling : CCS · 2022Review
- Translatome proteomics identifies autophagy as a resistance mechanism to on-target FLT3 inhibitors in acute myeloid leukemia.Leukemia · 2022Article
- Targeting EZH2 Promotes Chemosensitivity of BCL-2 Inhibitor through Suppressing PI3K and c-KIT Signaling in Acute Myeloid Leukemia.International journal of molecular sciences · 2022Article
- The dual role of autophagy in acute myeloid leukemia.Journal of hematology & oncology · 2022Review
- Article
- Lysosomes in Stem Cell Quiescence: A Potential Therapeutic Target in Acute Myeloid Leukemia.Cancers · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 8 institutions in 2 countries.
Funding
Abstract
Many cases of AML are associated with mutational activation of receptor tyrosine kinases (RTKs) such as FLT3. However, RTK inhibitors have limited clinical efficacy as single agents, indicating that AML is driven by concomitant activation of different signaling molecules. We used a functional genomic approach to identify RET, encoding an RTK, as an essential gene in multiple subtypes of AML, and observed that AML cells show activation of RET signaling via ARTN/GFRA3 and NRTN/GFRA2 ligand/co-receptor complexes. Interrogation of downstream pathways identified mTORC1-mediated suppression of autophagy and subsequent stabilization of leukemogenic drivers such as mutant FLT3 as important RET effectors. Accordingly, genetic or pharmacologic RET inhibition impaired the growth of FLT3-dependent AML cell lines and was accompanied by upregulation of autophagy and FLT3 depletion. RET dependence was also evident in mouse models of AML and primary AML patient samples, and transcriptome and immunohistochemistry analyses identified elevated RET mRNA levels and co-expression of RET and FLT3 proteins in a substantial proportion of AML patients. Our results indicate that RET-mTORC1 signaling promotes AML through autophagy suppression, suggesting that targeting RET or, more broadly, depletion of leukemogenic drivers via autophagy induction provides a therapeutic opportunity in a relevant subset of AML patients.
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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.