Bone marrow-like viscosity affects imatinib resistance in chronic myeloid leukemia

Chronic myeloid leukemia (CML), one type of blood cancer, is a clonal myeloproliferative disorder of hematopoietic stem cells that originated from bone marrow (BM). Imatinib (IM) resistance in CML treatment has been frequently reported, which mainly results from the complex microenvironment of BM. BM is a viscous tissue where cells are mechanically responsive to both the stiffness of matrices and the viscosity of surrounding fluid. Although the effect of stiffness on CML drug resistance has been revealed, the role of BM viscosity on IM resistance in CML is unclear. In this study, a BM-like viscous culture medium was prepared to investigate the effect of microenvironmental viscosity on IM resistance in CML cells. The culture media with viscosity ranging from 47.6 to 634.9 cP were prepared to establish viscosity-controlled culture media covering the reported physiological range of bone marrow and extending into an exploratory higher-viscosity condition. CML cells were suspended and cultured in the viscous culture media added or without addition of IM for 48 or 72 h. Cell viability decreased with IM concentration but increased with microenvironmental viscosity. The results suggested that increased microenvironmental viscosity reduced the sensitivity of CML cells to IM. The possible mechanism might involve the upregulated expression of IM resistance-related genes, reduced apoptosis rates, and altered expression patterns of the BCR::ABL1 gene.