Secretion of IL‐1β from imatinib‐resistant chronic myeloid leukemia cells contributes to BCR–ABL mutation‐independent imatinib resistance

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-1 beta (IL-1 beta) was more highly expressed in K562R than in the parental cell line K562S, and higher levels of IL-1b contributed to the imatinib resistance of K562R. In addition, IL-1 beta secreted from K562R cells affected stromal cell production of CXCL11, which in turn promoted migration of K562R cells into the stroma. Thus, elevated IL-1 beta production from TKI-resistant K562R cells may contribute to TKI resistance by increasing cell viability and promoting cell migration.