Sustained Activation of Non-canonical NF-kB Signalling Drives Glycolytic Reprogramming in Doxorubicin-resistant DLBCL

The transcriptomic profiles of two resistant (HT and OCI-LY3) and two sensitive (SUDHL5 and OCI-LY19) DLBCL cell lines before and after doxorubicin treatment were analysed by RNA-seq. To further investigate the molecular basis underlying the development of doxorubicin resistance, acquired doxorubicin-resistant cells (OCI-LY19R) were generated by periodically treating the parental doxorubicin-sensitive OCI-LY19 cells (OCI-LY19S) with increasing doses of doxorubicin over a prolonged period till its IC50 exceeded 200 nM. RNA-seq analysis was then performed using OCI-LY19R and OCI-LY19S cell lines to examine the transcriptomic changes following acquisition of doxorubicin resistance. Overall design: HT, OCI-LY3, SUDHL5 and OCI-LY19 cell lines with or without 0.2 uM doxorubicin exposure for 24h were harvested for RNA-seq analysis. Parental doxorubicin-sensitive cells (OCI-LY19S) and acquired doxorubicin-resistant cells (OCI-LY19R) were also harvested for RNA-seq analysis. Each sample was obtained from three independent experiments.