Abstract
Some cases of chronic myelogenous leukemia are resistant to tyrosine kinase inhibitors (TKIs) independently of mutation in BCR-ABL, but the detailed mechanism underlying this resistance has not yet been elucidated. In this study, we generated a TKI-resistant CML cell line, K562R, that lacks a mutation in BCR-ABL. Interleukin-1β (IL-1β) was more highly expressed in K562R than in the parental cell line K562S, and higher levels of IL-1β contributed to the imatinib resistance of K562R. In addition, IL-1β secreted from K562R cells affected stromal cell production of CXCL11, which in turn promoted migration of K562R cells into the stroma. Thus, elevated IL-1β production from TKI-resistant K562R cells may contribute to TKI resistance by increasing cell viability and promoting cell migration.
Keywords:
BCR-ABL; chronic myeloid leukemia; resistance; tyrosine kinase inhibitor.
© 2016 Federation of European Biochemical Societies.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects
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Cell Line
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Cell Movement / drug effects
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Chemokine CXCL11 / genetics
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Chemokine CXCL11 / metabolism
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Coculture Techniques
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Culture Media, Conditioned / metabolism
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Drug Resistance, Neoplasm*
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Fusion Proteins, bcr-abl / genetics
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Fusion Proteins, bcr-abl / metabolism*
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Imatinib Mesylate / pharmacology*
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Interleukin-1beta / genetics
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Interleukin-1beta / metabolism*
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K562 Cells
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
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Mutation
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Neoplasm Proteins / metabolism
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Protein Kinase Inhibitors / pharmacology*
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Stromal Cells / metabolism
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Up-Regulation*
Substances
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Antineoplastic Agents
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BCR-ABL1 fusion protein, human
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CXCL11 protein, human
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Chemokine CXCL11
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Culture Media, Conditioned
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IL1B protein, human
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Interleukin-1beta
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Neoplasm Proteins
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Protein Kinase Inhibitors
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Imatinib Mesylate
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Fusion Proteins, bcr-abl