ArticleBlood2020
Glucocorticoids enhance the antileukemic activity of FLT3 inhibitors in FLT3-mutant acute myeloid leukemia.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Rapid Transcription Dynamics Confers Cytarabine Resistance in Acute Myeloid Leukemia.Blood cancer discovery · 2026Article
- Quantitative proteomics and phosphoproteomics reveal glucocorticoid stimulation of TLR and Rho GTPase signaling in neutrophil-like cells.Genome biology · 2026Article
- Drug-tolerant persister cells: the deadly survivors in hematological malignancies.Frontiers in pharmacology · 2026Review
- Drug-tolerant persister cells in lymphoid malignancies: from mechanisms to therapeutic opportunities.Frontiers in oncology · 2026Review
- Article
- Comparative Analysis of the Therapeutic Efficacy of Decitabine Combined with Cytarabine, Aclarubicin, and Granulocyte Colony-stimulating Factor (D-CAG) Versus CAG Regimen in the Treatment of Acute Myeloid Leukemia.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2025Article
- Drug-induced tolerant persisters in tumor: mechanism, vulnerability and perspective implication for clinical treatment.Molecular cancer · 2025Review
- Inflammatory signaling pathways play a role in SYK inhibitor resistant AML.Scientific reports · 2025Article
- Inhibition of NLRP3 enhances pro-apoptotic effects of FLT3 inhibition in AML.Cell communication and signaling : CCS · 2025Article
- Drug-tolerant persister cells in acute myeloid leukemia: pressing challenge and promising new strategies for treatment.Frontiers in medicine · 2025Review
- The Effects of Resveratrol, Gallic Acid, and Piperine on the Expression of miR-17, miR-92b, miR-181a, miR-222, BAX, BCL-2, MCL-1, WT1, c-Kit, and CEBPA in Human Acute Myeloid Leukemia Cells and Their Roles in Apoptosis.Biochemical genetics · 2024Article
- Developments of Fms-like Tyrosine Kinase 3 Inhibitors as Anticancer Agents for AML Treatment.Current medicinal chemistry · 2024Review
- [Progress in molecular mechanisms and targeted therapies of persistent cancer cells].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2023Article
- Long non-coding RNAs regulate treatment outcome in leukemia: What have we learnt recently?Cancer medicine · 2023Review
- Dexamethasone enhances venetoclax-induced apoptosis in acute myeloid leukemia cells.Medical oncology (Northwood, London, England) · 2023Article
- Targeting C/EBPα overcomes primary resistance and improves the efficacy of FLT3 inhibitors in acute myeloid leukaemia.Nature communications · 2023Article
- Inflammatory response mediates cross-talk with immune function and reveals clinical features in acute myeloid leukemia.Bioscience reports · 2022Article
- The FLT3 Y842D mutation may be highly sensitive to midostaurin: a case report.The Journal of international medical research · 2022Article
- The glucocorticoid receptor associates with the cohesin loader NIPBL to promote long-range gene regulation.Science advances · 2022Article
- Acute Myeloid Leukemia Stem Cells: Origin, Characteristics, and Clinical Implications.Stem cell reviews and reports · 2022Review
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
FLT3 is a frequently mutated gene that is highly associated with a poor prognosis in acute myeloid leukemia (AML). Despite initially responding to FLT3 inhibitors, most patients eventually relapse with drug resistance. The mechanism by which resistance arises and the initial response to drug treatment that promotes cell survival is unknown. Recent studies show that a transiently maintained subpopulation of drug-sensitive cells, so-called drug-tolerant "persisters" (DTPs), can survive cytotoxic drug exposure despite lacking resistance-conferring mutations. Using RNA sequencing and drug screening, we find that treatment of FLT3 internal tandem duplication AML cells with quizartinib, a selective FLT3 inhibitor, upregulates inflammatory genes in DTPs and thereby confers susceptibility to anti-inflammatory glucocorticoids (GCs). Mechanistically, the combination of FLT3 inhibitors and GCs enhances cell death of FLT3 mutant, but not wild-type, cells through GC-receptor-dependent upregulation of the proapoptotic protein BIM and proteasomal degradation of the antiapoptotic protein MCL-1. Moreover, the enhanced antileukemic activity by quizartinib and dexamethasone combination has been validated using primary AML patient samples and xenograft mouse models. Collectively, our study indicates that the combination of FLT3 inhibitors and GCs has the potential to eliminate DTPs and therefore prevent minimal residual disease, mutational drug resistance, and relapse in FLT3-mutant AML.
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Registered trials
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