Purpose of review Glucocorticoids
remain a central component of the therapeutic armamentarium for a broad spectrum of hematologic malignancies. There is an extensive body of evidence suggesting that the efficacy of glucocorticoids
stems from their ability to mediate apoptosis
in leukemia, lymphoma, and myeloma cells.
Traditionally, glucocorticoid-induced apoptosis
is divided into three stages: an initiation stage, which involves glucocorticoid receptor
activation and glucocorticoid receptor
-mediated gene regulation; a decision stage, which engages the prosurvival and proapoptotic factors at the mitochondrial level; and an execution stage, which implicates caspases
and endonuclease activation. Recent discoveries have clarified many aspects of the apoptotic pathway, including activation of the caspases
cascade and multicatalytic proteasome, suppression of prosurvival transcription factors such as AP-1, c-myc, nuclear factor-κB, as well as cross-talk between the T-cell receptor and cytokine signaling pathways.
This review focuses primarily on insights gained during recent years into the mechanism of the signaling pathways responsible for mediating glucocorticoid-induced apoptosis
in hematologic malignancies. This information provides a scientific basis to explore synergistic approaches that may enhance glucocorticoid-induced apoptosis
and may bypass mechanism of resistance.