ArticleBlood2021
Depalmitoylation rewires FLT3-ITD signaling and exacerbates leukemia progression.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Efficacy and safety of FLT3 inhibitors in monotherapy of hematological and solid malignancies: a systemic analysis of clinical trials.Frontiers in pharmacology · 2024Pooled it
- The role of protein palmitoylation in disease pathogenesis and therapeutic innovation.Annals of medicine · 2026Review
- Article
- The functional roles and therapeutic potential of protein palmitoylation in hepatocellular carcinoma.Discover oncology · 2026Review
- Reprogramming lipid metabolism in pediatric cancers.Oncogenesis · 2026Review
- Superior response and survival of intensive chemotherapy over venetoclax plus azacitidine in newly diagnosed KIT-mutated acute myeloid leukemia.Annals of hematology · 2026Article
- TIP-20, a novel feline McDonough sarcoma-like tyrosine kinase 3 inhibitor with potent antileukemia activity.The Journal of international medical research · 2026Article
- Protein palmitoylation in hematological malignancies: mechanistic links to lipid metabolic reprogramming and therapy resistance.Frontiers in immunology · 2026Review
- Golgi Retention and Oncogenic Signaling of KIT Tyrosine Kinase in Gastrointestinal Stromal Tumor.Sub-cellular biochemistry · 2026Review
- From EGFR PTM network to TKI resistance: spatial subtypes and targeting in lung cancer.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Targeting p16Leukemia · 2025Article
- Unveiling the Genetic Mosaic of Pediatric AML: Insights from Southwest China.Current oncology (Toronto, Ont.) · 2025Article
- Protein palmitoylation in hepatic diseases: Functional insights and therapeutic strategies.Journal of advanced research · 2025Review
- Recent advances in S-palmitoylation and its emerging roles in human diseases.Journal of hematology & oncology · 2025Review
- Impact of FLT3 mutation on its intracellular localization and implications for anti-leukemia strategy.Annals of hematology · 2025Review
- Downregulation of S6 Kinase and Hedgehog-Gli1 by Inhibition of Fatty Acid Synthase in AML with FLT3-ITD Mutation.International journal of molecular sciences · 2025Article
- Multi-omics integration reveals immune hallmarks and biomarkers associated with FLT3 inhibitor sensitivity in FLT3-mutated AML.Blood science (Baltimore, Md.) · 2025Article
- Palmitoylation in cardiovascular diseases: Molecular mechanism and therapeutic potential.International journal of cardiology. Heart & vasculature · 2025Review
- Article
- Decursin induces FLT3-ITD acute myeloid leukemia cell apoptosis by increasing the expression of the ubiquitin-conjugase UBE2L6.Cell communication and signaling : CCS · 2025Article
Corrections and comments
- Commented on by
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Internal tandem duplication within FLT3 (FLT3-ITD) is one of the most frequent mutations in acute myeloid leukemia (AML) and correlates with a poor prognosis. Whereas the FLT3 receptor tyrosine kinase is activated at the plasma membrane to transduce PI3K/AKT and RAS/MAPK signaling, FLT3-ITD resides in the endoplasmic reticulum and triggers constitutive STAT5 phosphorylation. Mechanisms underlying this aberrant FLT3-ITD subcellular localization or its impact on leukemogenesis remain poorly established. In this study, we discovered that FLT3-ITD is S-palmitoylated by the palmitoyl acyltransferase ZDHHC6. Disruption of palmitoylation redirected FLT3-ITD to the plasma membrane and rewired its downstream signaling by activating AKT and extracellular signal-regulated kinase pathways in addition to STAT5. Consequently, abrogation of palmitoylation increased FLT3-ITD-mediated progression of leukemia in xenotransplant-recipient mouse models. We further demonstrate that FLT3 proteins were palmitoylated in primary human AML cells. ZDHHC6-mediated palmitoylation restrained FLT3-ITD surface expression, signaling, and colonogenic growth of primary FLT3-ITD+ AML. More important, pharmacological inhibition of FLT3-ITD depalmitoylation synergized with the US Food and Drug Administration-approved FLT3 kinase inhibitor gilteritinib in abrogating the growth of primary FLT3-ITD+ AML cells. These findings provide novel insights into lipid-dependent compartmentalization of FLT3-ITD signaling in AML and suggest targeting depalmitoylation as a new therapeutic strategy to treat FLT3-ITD+ leukemias.
Indexed as
Identifiers
What OpenQuestion holds
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.