Effects of ERK5 Pathway Inhibition on the Progenitor Cell Potential of CML Cell Lines
(A) Effects of MEK5/ERK5 inhibitors on CRA. Kinetics of repopulation of drug-free normoxic secondary cultures (LC2) established with KCL22 or K562 cells rescued from primary cultures (LC1) incubated in 0.1% O2 and treated for 7 days with DMSO (Vehicle) or the indicated inhibitors. Values are means ± SD of three independent experiments. Differences between drug- and vehicle-treated cultures were significant (p ≤ 0.01) from day 21 (KCL22) or day 17 (K562) on for BIX02189, and from day 14 (KCL22) or day 10 (K562) on for XMD8-92.
(B and C) Effects of ERK5 genetic inhibition in K562 cells on cell number and CRA. (B) Cells transduced with (inset) non-targeting control (shNT) or two different ERK5-targeting shRNA (shERK5-1, shERK5-2) were incubated in 0.1% O2 and viable cells counted at the indicated times of LC1. ∗p ≤ 0.05 versus shNT at the same time point. (C) LC2 repopulation by cells from day 7 LC1 shown in (B). Values are means ± SD of three independent experiments. Differences between shERK5-1 or shERK5-2 with respect to the shNT control were significant (p < 0.05) from day 24 on.