Sequential gene regulatory events leading to glucocorticoid-evoked apoptosis of CEM human leukemic cells:interactions of MAPK, MYC and glucocorticoid pathways.

Gene expression responses to glucocorticoid (GC) in the hours preceding onset of apoptosis were compared in three clones of human acute lymphoblastic leukemia CEM cells. Between 2 and 20h, all three clones showed increasing numbers of responding genes. Each clone had many unique responses, but the two responsive clones showed a group of responding genes in common, different from the resistant clone. MYC levels and the balance of activities between the three major groups of MAPKs are known important regulators of glucocorticoid-driven apoptosis in several lymphoid cell systems. Common to the two sensitive clones were changed transcript levels from genes that decrease amounts or activity of anti-apoptotic ERK/MAPK1 and JNK2/MAPK9, or of genes that increase activity of pro-apoptotic p38/MAPK14. Down-regulation of MYC and several MYC-regulated genes relevant to MAPKs also occurred in both sensitive clones. Transcriptomine comparisons revealed probable NOTCH-GC crosstalk in these cells.