Despite inhibition of BCR-ABL1 kinase imatinib does not reduce ROS and oxidative DNA damage in LSCs and LPCs to the levels observed in normal counterparts. (A-C) Lin⁻CD34⁺ cells from healthy donors and CML-CP patients were untreated (black and gray bars, respectively) or treated with 1 μM imatinib (white corresponding bars) for 48 hours (2 doses at time points 0 and 24 hours) in the presence of a growth factor cocktail. Annexin V–negative (A) Lin⁻CD34⁺CD38⁻CFSE^max/CTV^max quiescent HSCs/LSCs, (B) Lin⁻CD34⁺CD38⁻ HSCs/LSCs, and (C) Lin⁻CD34⁺CD38⁺ early HPCs/LPCs were examined for BCR-ABL1 kinase activity (immunofluorescent detection of ABL1-pY245), ROS (fluorescent detection of H₂O₂ and ·OH by DCFDA), and oxidative DNA damage (8-oxoG and γ-H2AX = DSBs). Results represent mean ± SD from 5 to 20 healthy donors/patients; *P < .01 in comparison with untreated normal cells, **P < .05 in comparison with untreated CML-CP cells and normal cells, and ***P < .05 in comparison with untreated CML-CP cells. (D-F) Lin⁻CD34⁺ cells harvested at diagnosis from 6 CML-CP good responders (GR) and 4 poor responders (PR) were treated (+) or not (−) with 1 μM imatinib for 48 hours (2 doses at time points 0 and 24 hours) in the presence of a growth factor cocktail. (D) Lin⁻CD34⁺CD38⁻CFSE^max/CTV^max quiescent LSCs, (E) Lin⁻CD34⁺CD38⁻ LSCs, and (F) Lin⁻CD34⁺CD38⁺ early LPCs were examined for ROS (DCFDA), and oxidative DNA damage (8-oxoG and γ-H2AX). Results represent mean ± SD; *P < .05 in comparison with corresponding GR sample.