Effects of polymorphisms in NR1I2, CYP3A4, and ABC transporters on the steady-state plasma trough concentrations of bosutinib in Japanese patient with chronic myeloid leukemia.
Dasatinib (DAS) is a tyrosine kinase inhibitor (TKI) used in the treatment of chronic myeloid leukemia and in the management of ulcerative colitis (UC).Since some nutraceuticals (e.g. curcumin, olive oil, and cocoa extract) could alter the function of ABC transporters and /or CYP450 enzymes, DAS bioavailability could potentially be affected following their co-administration.
Despite the enormous success of imatinib in chronic myeloid leukemia (CML), therapy resistance has emerged in a significant proportion of patients, partly because of the overexpression of ABC efflux transporters.
Taken together, our findings support a model in which c-MYC-driven transcriptional events, combined with epigenetic mechanisms, direct and regulate the expression of ABC genes with possible implications in tumor malignancy and drug efflux in CML.
Therefore, our evidence suggests for the role of ABC transporters in resistance to TKI on primitive HSCs and CML stem cells and provides a rationale how TKI resistance can be overcome in vivo.
Soluble class I molecules (sHLA-ABC) were measured by an enzyme-linked immunosorbent assay (ELISA) in plasma samples of 13 patients with chronic-phase Ph1-positive chronic myelogenous leukemia (CML).