Lee Cho-Rong, Kang Jung-Ah, Kim Hye-Eun, Choi Yegyun, Yang Taewoo, Park Sung-Gyoo
School of Life Sciences, Gwangju Institute of Science and Technology, Korea.
FEBS Lett. 2016 Feb;590(3):358-68. doi: 10.1002/1873-3468.12057. Epub 2016 Jan 25.
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.
一些慢性粒细胞白血病病例对酪氨酸激酶抑制剂（TKIs）耐药，且与BCR-ABL突变无关，但这种耐药的详细机制尚未阐明。在本研究中，我们构建了一种对TKI耐药的慢性粒细胞白血病细胞系K562R，其BCR-ABL无突变。白细胞介素-1β（IL-1β）在K562R中的表达高于亲本细胞系K562S，且较高水平的IL-1β导致K562R对伊马替尼耐药。此外，K562R细胞分泌的IL-1β影响基质细胞CXCL11的产生，进而促进K562R细胞向基质迁移。因此，TKI耐药的K562R细胞中IL-1β产生增加可能通过提高细胞活力和促进细胞迁移导致TKI耐药。
