ArticleBlood cancer journal2015
Drug screen in patient cells suggests quinacrine to be repositioned for treatment of acute myeloid leukemia.
Article in Blood cancer journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 57 citations in OpenAlex.
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- Similarity-assisted variational autoencoder for nonlinear dimension reduction with application to single-cell RNA sequencing data.BMC bioinformatics · 2023Article
- Application of Drug Repurposing-Based Precision Medicine Platform for Leukaemia Patient Treatment.Advances in experimental medicine and biology · 2023Review
- Identification of curaxin as a potential new therapeutic for JAK2 V617F mutant patients.PloS one · 2023Article
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- 9-Aminoacridine Inhibits Ribosome Biogenesis by Targeting Both Transcription and Processing of Ribosomal RNA.International journal of molecular sciences · 2022Article
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- Quinacrine-CASIN combination overcomes chemoresistance in human acute lymphoid leukemia.Nature communications · 2021Article
- Quinacrine Induces Nucleolar Stress in Treatment-Refractory Ovarian Cancer Cell Lines.Cancers · 2021Article
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- Quinacrine Has Preferential Anticancer Effects on Mesothelioma Cells With Inactivating NF2 Mutations.Frontiers in pharmacology · 2021Article
- Selective killing of homologous recombination-deficient cancer cell lines by inhibitors of the RPA:RAD52 protein-protein interaction.PloS one · 2021Article
- A Drug Repositioning Approach Identifies a Combination of Compounds as a Potential Regimen for Chronic Lymphocytic Leukemia Treatment.Frontiers in oncology · 2021Article
- Has Drug Repurposing Fulfilled its Promise in Acute Myeloid Leukaemia?Journal of clinical medicine · 2020Review
- Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To find drugs suitable for repositioning for use against leukemia, samples from patients with chronic lymphocytic, acute myeloid and lymphocytic leukemias as well as peripheral blood mononuclear cells (PBMC) were tested in response to 1266 compounds from the LOPAC(1280) library (Sigma). Twenty-five compounds were defined as hits with activity in all leukemia subgroups (<50% cell survival compared with control) at 10 μM drug concentration. Only one of these compounds, quinacrine, showed low activity in normal PBMCs and was therefore selected for further preclinical evaluation. Mining the NCI-60 and the NextBio databases demonstrated leukemia sensitivity and the ability of quinacrine to reverse myeloid leukemia gene expression. Mechanistic exploration was performed using the NextBio bioinformatic software using gene expression analysis of drug exposed acute myeloid leukemia cultures (HL-60) in the database. Analysis of gene enrichment and drug correlations revealed strong connections to ribosomal biogenesis nucleoli and translation initiation. The highest drug-drug correlation was to ellipticine, a known RNA polymerase I inhibitor. These results were validated by additional gene expression analysis performed in-house. Quinacrine induced early inhibition of protein synthesis supporting these predictions. The results suggest that quinacrine have repositioning potential for treatment of acute myeloid leukemia by targeting of ribosomal biogenesis.
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