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.