Differentiation status of primary chronic myeloid leukemia cells affects sensitivity to BCR-ABL1 inhibitors.

ABSTRACT: Tyrosine kinase inhibitors (TKI) are the mainstay treatment of BCR-ABL1-positive leukemia and virtually all patients with chronic myeloid leukemia in chronic phase (CP CML) respond to TKI therapy. However, there is limited information on the cellular mechanisms of response and particularly on the effect of cell differentiation state to TKI sensitivity in vivo and ex vivo/in vitro. We used multiple, independent high-throughput drug sensitivity and resistance testing platforms that collectively evaluated 295 oncology compounds to characterize ex vivo drug response profiles of primary cells freshly collected from newly-diagnosed patients with BCR-ABL1-positive leukemia (n = 40) and healthy controls (n = 12). In contrast to the highly TKI-sensitive cells from blast phase CML and Philadelphia c

SUBMITTER: Pietarinen PO 

PROVIDER: S-EPMC5410248 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature