Comparative computational methods for identification of inherent or acquired mechanisms of resistance to prednisolone in Acute Lymphoblastic Leukemia cells

It has been shown previously that glucocorticoids exert a dual mechanism of action, meaning cytotoxic and mitogenic as well as mitogenic and anti-apoptotic, in a dose-dependent manner on CCRF-CEM cells at 72 h. Early gene expression response suggested also a dose-dependent dual mechanism of action of prednisolone which is apparently reflected on cell state upon 72 h of treatment. The present work applies different computational methods on microarray data in order to examine the hypothesis whether these cells have an intrinsic or acquired mechanism of resistance. Early onset gene expression at 4 h was compared to 72 h gene expression. Early gene expression allowed identification of genes initiating pivotal, early onset regulatory mechanisms activated by prednisolone. Late, 72 h exposure, microarray analysis allowed the relative identification of feedback mechanisms. From these results, it appears that CCRF-CEM cells used in this study exhibited a combined pattern of intrinsic and acquired resistance to prednisolone.