Fig. 2

CHEK1 is a marker for high-risk MM and induces drug resistance. A Heatmap of RNA-seq data showing significantly differentiated genes before and after doxycycline-induced CHEK1 OE. B Pathway enrichment analysis of RNA-seq data revealed enrichment of two pathways, which were related to cell cycle regulation and osteoclast differentiation. C Box plot representing CHEK1 expression in eight MM risk subgroups from the TT2 patient cohort. D In paired patient MM samples collected at first diagnosis and relapse, CHEK1 mRNA expression was increased in the relapsed samples relative to the corresponding samples from first diagnosis. E–F Increased CHEK1 expression was correlated with decreased OS in relapsed patients from the (E) TT2 and (F) APEX cohorts. G Western blotting confirmed that CHEK1 protein levels were significantly increased in MM1.R (dexamethasone-resistant) and ANBL6 DR (Bortezomib-resistant) cells. H Effects of Bortezomib and Adriamycin on the cell viability of H929 and ARP1 cells with or without CHEK1 OE. I Western blots demonstrated that CHEK1 OE induced resistance to Adriamycin and Bortezomib in ARP1 and H929 cells, as indicated by cleavage of the apoptotic regulators PARP and Caspase 3. J–K Pro-apoptotic effects of (J) CHEK1 shRNA silencing and the (K) CHEK1 selective inhibitor LY2603618 in H929 and ARP1 cells, as demonstrated by increased cleavage of PARP and Caspase 3