title: Secretion of IL-1β from imatinib-resistant chronic myeloid leukemia cells contributes to BCR-ABL mutation-independent imatinib resistance.
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.
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Korea.
authors.forename: Cho-Rong
authors.initials: CR
authors.lastname: Lee
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Korea.
authors.forename: Jung-Ah
authors.initials: JA
authors.lastname: Kang
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Korea.
authors.forename: Hye-Eun
authors.initials: HE
authors.lastname: Kim
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Korea.
authors.forename: Yegyun
authors.initials: Y
authors.lastname: Choi
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Korea.
authors.forename: Taewoo
authors.initials: T
authors.lastname: Yang
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Korea.
authors.forename: Sung-Gyoo
authors.initials: SG
authors.lastname: Park
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D054371:Chemokine CXCL11 / Q000235:genetics / Q000378:metabolism; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000068877:Imatinib Mesylate / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017154:Stromal Cells / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; C581634:BCR-ABL1 fusion protein, human; C515202:CXCL11 protein, human; D054371:Chemokine CXCL11; D017077:Culture Media, Conditioned; C508585:IL1B protein, human; D053583:Interleukin-1beta; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl
keywords: BCR-ABL; chronic myeloid leukemia; resistance; tyrosine kinase inhibitor