ArticleCarcinogenesis2012
Overcoming CML acquired resistance by specific inhibition of Aurora A kinase in the KCL-22 cell model.
Article in Carcinogenesis, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Emerging roles of Aurora-A kinase in cancer therapy resistance.Acta pharmaceutica Sinica. B · 2023Review
- Targeting SOS1 overcomes imatinib resistance with BCR-ABL independence through uptake transporter SLC22A4 in CML.Molecular therapy oncolytics · 2021Article
- Hyper-activation of Aurora kinase a-polo-like kinase 1-FOXM1 axis promotes chronic myeloid leukemia resistance to tyrosine kinase inhibitors.Journal of experimental & clinical cancer research : CR · 2019Article
- Bardet-Biedl Syndrome proteins regulate cilia disassembly during tissue maturation.Cellular and molecular life sciences : CMLS · 2019Article
- Aurora kinases: novel therapy targets in cancers.Oncotarget · 2017Review
- Aurora A Kinase Inhibitor AKI603 Induces Cellular Senescence in Chronic Myeloid Leukemia Cells Harboring T315I Mutation.Scientific reports · 2016Article
- Natural-Based Indirubins Display Potent Cytotoxicity toward Wild-Type and T315I-Resistant Leukemia Cell Lines.Journal of natural products · 2016Article
- A MYC-aurora kinase A protein complex represents an actionable drug target in p53-altered liver cancer.Nature medicine · 2016Article
- The aurora kinases in cell cycle and leukemia.Oncogene · 2015Review
- A delay prior to mitotic entry triggers caspase 8-dependent cell death in p53-deficient Hela and HCT-116 cells.Cell cycle (Georgetown, Tex.) · 2015Article
- ATRA-induced cellular differentiation and CD38 expression inhibits acquisition of BCR-ABL mutations for CML acquired resistance.PLoS genetics · 2014Article
- Article
- Stathmin and microtubules regulate mitotic entry in HeLa cells by controlling activation of both Aurora kinase A and Plk1.Molecular biology of the cell · 2013Article
- Pediatric relapsed or refractory leukemia: new pharmacotherapeutic developments and future directions.Drugs · 2013Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Serine/threonine kinase Aurora A is essential for regulating mammalian cell division and is overexpressed in many types of human cancer. However, the role of Aurora A in chemoresistance of chronic myelogenous leukemia (CML) is not well understood. Using the KCL-22 cell culture model we have recently developed for studying mechanisms of CML acquired resistance, we found that Aurora A expression was partially reduced in these cells upon treatment with the tyrosine kinase inhibitor imatinib, which accompanied the acquisition of BCR-ABL mutation for imatinib resistance. Gene knockdown of BCR-ABL also reduced Aurora A expression, and conversely, Aurora A expression increased in hematopoietic progenitor cells after BCR-ABL expression. Inhibition of Aurora A induced apoptosis of CML cells with or without T315I BCR-ABL mutation and suppressed CML cell growth. Inhibition of Aurora A by gene knockdown or a highly specific small molecule inhibitor sensitized CML cells to imatinib treatment and effectively blocked acquisition of BCR-ABL mutations and KCL-22 cell relapse on imatinib, nilotinib or dasatinib. Our results show that Aurora A plays an important role for facilitating acquisition of BCR-ABL mutation and acquired resistance to tyrosine kinase inhibitors in the culture model and suggest that inhibition of Aurora A may provide an alternative strategy to improve CML treatment to overcome resistance.
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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.