ArticleBlood2012
Fluvastatin inhibits FLT3 glycosylation in human and murine cells and prolongs survival of mice with FLT3/ITD leukemia.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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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.
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Who cites it
44 citing papers in PubMed, 75 citations in OpenAlex.
- Report of the relapsed/refractory cohort of SWOG S0919: A phase 2 study of idarubicin and cytarabine in combination with pravastatin for acute myelogenous leukemia (AML).Leukemia research · 2018Trial
- SWOG0919: a Phase 2 study of idarubicin and cytarabine in combination with pravastatin for relapsed acute myeloid leukaemia.British journal of haematology · 2014Trial
- Reawakening Differentiation Therapy in Acute Myeloid Leukemia: A Comprehensive Review of ATRA-Based Combination Strategies.Current oncology (Toronto, Ont.) · 2026Review
- Golgi Retention and Oncogenic Signaling of KIT Tyrosine Kinase in Gastrointestinal Stromal Tumor.Sub-cellular biochemistry · 2026Review
- Statins induce monocytic differentiation in acute myeloid leukemia cells through the KLF4/DPYSL2A axis.FEBS open bio · 2025Article
- Review
- Impact of FLT3 mutation on its intracellular localization and implications for anti-leukemia strategy.Annals of hematology · 2025Review
- Vitamin K1 Induced Cytotoxic Effects and Transcriptomic Analysis in Jurkat T Lymphocyte Leukemia Cells.Cancer management and research · 2025Article
- Glycosylation: mechanisms, biological functions and clinical implications.Signal transduction and targeted therapy · 2024Review
- Importance of PTM of FLT3 in acute myeloid leukemia.Acta biochimica et biophysica Sinica · 2024Review
- BRCC36 associates with FLT3-ITD to regulate its protein stability and intracellular signaling in acute myeloid leukemia.Cancer science · 2024Article
- Simvastatin Preferentially Targets FLT3/ITD Acute Myeloid Leukemia by Inhibiting MEK/ERK and p38-MAPK Signaling Pathways.Drugs in R&D · 2023Article
- NADPH oxidase mediated oxidative stress signaling in FLT3-ITD acute myeloid leukemia.Cell death discovery · 2023Review
- Mannose metabolism inhibition sensitizes acute myeloid leukaemia cells to therapy by driving ferroptotic cell death.Nature communications · 2023Article
- Article
- FLT3-ITD transduces autonomous growth signals during its biosynthetic trafficking in acute myelogenous leukemia cells.Scientific reports · 2021Article
- IntegratedCells · 2021Article
- Article
- Genomic Abnormalities as Biomarkers and Therapeutic Targets in Acute Myeloid Leukemia.Cancers · 2021Review
- Actin cytoskeleton deregulation confers midostaurin resistance in FLT3-mutant acute myeloid leukemia.Communications biology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
FLT3 is frequently mutated in acute myeloid leukemia (AML), but resistance has limited the benefit of tyrosine kinase inhibitors (TKI). We demonstrate that statins can impair FLT3 glycosylation, thus leading to loss of surface expression and induction of cell death, as well as mitigation of TKI resistance. Immunofluorescence microscopy confirms a reduction in surface localization and an increase in intracellular FLT3/internal tandem duplication (ITD) accumulation. This aberrant localization was associated with increased STAT5 activation but inhibition of both MAPK and AKT phosphorylation. Growth inhibition studies indicate that FLT3/ITD-expressing cells were killed with an IC(50) within a range of 0.2-2μM fluvastatin. Several mechanisms of resistance could be circumvented by fluvastatin treatment. An increase in the IC(50) for inhibition of phosphorylated FLT3/ITD by lestaurtinib caused by exogenous FLT3 ligand, resistance to sorafenib caused by the D835Y or FLT3/ITD N676K mutations, and activation of the IL-3 compensatory pathway were all negated by fluvastatin treatment. Finally, fluvastatin treatment in vivo reduced engraftment of BaF3 FLT3/ITD cells in Balb/c mice. These results demonstrate that statins, a class of drugs already approved by the US Food and Drug Administration, might be repurposed for the management of FLT3 mutant acute myeloid leukemia cases either alone or in conjunction with FLT3 TKI.
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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.