Fig. 1

The up-modulation and hyper-activation of Aurora A/PLK1/FOXM1 axis associated with IM resistance in BCR-ABL1+ cell lines. a-Aurora A expression and phosphorylation at T288 are significantly increased in IM-resistant K562 cells, and result in hyper-phosphorylation of its target, the histone H3 at S20. IM resistance is associated with the over-expression and hyper-activation of downstream signals: PLK1 and FOXM1; b-A significant increment of Aurora A, PLK1 and FOXM1 transcripts (p < 0.05 or less) supports that the over-expression of these three signals associated with drug resistance is partly contingent upon transcriptional events; c- Aurora A, PLK1 and FOXM1 phosphorylation is significantly reduced in response to IM, supporting their dependence from BCR-ABL1 TK; d- Aurora A expression and phosphorylation at T288 are significantly increased in IM-resistant 32Dp210 and BaF3p210 cells. IM resistance is associated with the over-expression and hyper-activation of downstream signals: PLK1 and FOXM1. A reduction of AURORA A, PLK1 and FOXM1 expression and activation was evident in IM-sensitive and IM-resistant cell lines in response to pan-AK inhibitor Danusertib (Dan), PLK1 inhibitor Volasertib (Vol) and FOXM1 inhibitor Thiostrepton (Thio); e,f-A likewise reduction of AURORA A, PLK1 and FOXM1 expression and activating phosphorylation was apparent in IM-sensitive and IM-resistant K562 in response to pan-AK inhibitor Danusertib (Dan), PLK1 inhibitor Volasertib (Vol) and FOXM1 inhibitor Thiostrepton (Thio); g,h-AURORA A inhibitory signal GADD45a is significantly raised in response to IM in IM-sensitive K562 cell line and to Dan, Vol and Thio both in IM-sensitive and IM-resistant K562 cells I-Apoptotic death induction in response to above mentioned drugs of IM-sensitive and IM-resistant K562 cells