Efficiency of nilotinib to target chronic phase-chronic myeloid leukaemia primary mature CD34^- and immature CD34⁺ cells.

ABSTRACT: Accumulation in target cells is an essential pharmacokinetic step of targeted therapies. Tyrosine Kinase Inhibitors (TKI) against the BCR-ABL fusion protein in Chronic Phase-Chronic Myeloid Leukaemia (CP-CML) cells constitute a unique model in terms of efficacy, specificity, and in vivo demonstration of response heterogeneity by target cells. The overall therapeutic response to nilotinib is heterogeneous with no satisfactory explanation. To better understand the patients' response heterogeneity, we quantified nilotinib uptake by primary CP-CML cells in standardized conditions using flow cytometry, which allowed also distinguishing mature (polymorphonuclear cells) from immature (CD34⁺) cells. Nilotinib was undetectable in 13.3% of PMN and 40% of CD34⁺ cells. Moreover,

SUBMITTER: Berger MG 

PROVIDER: S-EPMC7969931 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature