ArticleHaematologica2022
Genome-wide CRISPR screen identifies regulators of MAPK and MTOR pathways mediating sorafenib resistance in acute myeloid leukemia.
Article in Haematologica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Lactate metabolism and epigenetic reprogramming drive c-KIT hyperactivation to mediate Gilteritinib resistance: Rationale for c-KIT degraders over kinase inhibitors.Acta pharmaceutica Sinica. B · 2026Article
- Methylome profiling reveals context-dependent chemo-resistance mechanisms and enhances risk stratification in AML.Cancer cell international · 2026Article
- Crosstalk Between FOXN3 and E2F5 Reveals a Novel Tumor Suppressive Pathway in Acute Myeloid Leukemia via MAPK Signaling: Implications for Potential Future Targeted Therapy.Blood and lymphatic cancer : targets and therapy · 2026Article
- Assessment of Circulating Tumor DNA for Early Detection of Hepatocellular Carcinoma in Alpha-Fetoprotein-Negative Patients With Cirrhotic Nodules.JGH open : an open access journal of gastroenterology and hepatology · 2026Article
- Intrinsic resistance to RAS inhibitors is driven by dysregulation of KRAS degradation.Nature communications · 2025Article
- Clinicopathologic Characteristics and Prognostic Profile of Chronic Myeloid Neoplasms With Somatic NF1 Mutations in Adult Patients.European journal of haematology · 2025Article
- Unveiling Pharmacogenomics Insights into Circular RNAs: Toward Precision Medicine in Cancer Therapy.Biomolecules · 2025Review
- Review
- CRISPR screening in hematology research: from bulk to single-cell level.Journal of hematology & oncology · 2023Review
- Venetoclax Overcomes Sorafenib Resistance in Acute Myeloid Leukemia by Targeting BCL2.Biology · 2023Article
- Targeting C/EBPα overcomes primary resistance and improves the efficacy of FLT3 inhibitors in acute myeloid leukaemia.Nature communications · 2023Article
- A Receptor Tyrosine Kinase Inhibitor Sensitivity Prediction Model Identifies AXL Dependency in Leukemia.International journal of molecular sciences · 2023Article
- The GSK3β/Mcl-1 axis is regulated by both FLT3-ITD and Axl and determines the apoptosis induction abilities of FLT3-ITD inhibitors.Cell death discovery · 2023Article
- A Bayesian model for unsupervised detection of RNA splicing based subtypes in cancers.Nature communications · 2023Article
- Article
- Impaired Proteolysis of Noncanonical RAS Proteins Drives Clonal Hematopoietic Transformation.Cancer discovery · 2022Article
- Review
- CRISPR/Cas9 gene editing: a new approach for overcoming drug resistance in cancer.Cellular & molecular biology letters · 2022Review
- A Comprehensive Pan-Cancer Analysis of the Tumorigenic Effect of Leucine-Zipper-Like Transcription Regulator (LZTR1) in Human Cancer.Oxidative medicine and cellular longevity · 2022Article
- MicroRNA-138-1-3p sensitizes sorafenib to hepatocellular carcinoma by targeting PAK5 mediated β-catenin/ABCB1 signaling pathway.Journal of biomedical science · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Drug resistance impedes the long-term effect of targeted therapies in acute myeloid leukemia (AML), necessitating the identification of mechanisms underlying resistance. Approximately 25% of AML patients carry FLT3 mutations and develop post-treatment insensitivity to FLT3 inhibitors, including sorafenib. Using a genome-wide CRISPR screen, we identified LZTR1, NF1, TSC1 or TSC2, negative regulators of the MAPK and MTOR pathways, as mediators of sorafenib resistance. Analyses of ex vivo drug sensitivity assays in FLT3-ITD AML patient samples revealed lower expression of LZTR1, NF1, and TSC2 correlated with sorafenib sensitivity. Importantly, MAPK and/or MTOR complex1 (MTORC1) activity were upregulated in AML cells made resistant to several FLT3 inhibitors, including crenolanib, quizartinib, or sorafenib. These cells were sensitive to MEK inhibitors, and the combination of FLT3 and MEK inhibitors showed enhanced efficacy, suggesting its effectiveness in AML patients with FLT3 mutations and those with resistance to FLT3 inhibitors.
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Registered trials
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