Physical Sciences and Mathematics Commons^™

Role Of Bcl-2 Family Members To Promote Glucocorticoid –Induced Apoptosis By Mek Inhibitors In Leukemic Cells, Anila Rambal

Theses and Dissertations

Glucocorticoids (GC) are common components of many chemotherapeutic regimens for lymphoid malignancies. GC-induced apoptosis involves an intrinsic BCL-2 family-regulated pathway. It has been shown that BIM (BCL-2 interacting mediator of cell death), a BH3-only pro-apoptotic protein, is up-regulated by dexamethasone (Dex) treatment in acute lymphoblastic leukemia (ALL) cells. Furthermore, BIM is inactivated by extracellular signal-regulated kinase (ERK)-mediated phosphorylation. We therefore hypothesized co-treatment with Dex and MEK/ERK inhibitors would promote apoptosis in ALL cells through BIM up-regulation and activation. We show here that a MEK inhibitor, PD184352 synergistically enhances Dex lethality in CCRF-CEM (T-ALL) cells. Co-treatment with Dex and PD184352 results …