Promyelocytic leukemia zinc finger protein [PLZF] enhances glucocorticoid-induced apoptosis in leukemic cell line NALM6

ABSTRACT

Glucocorticoids [GC] actuate apoptosis as well as cell cycle arrest in lymphocytes, and included as core element in the lymphoid malignancy treatment. Despite clinical significance of GC and considerable efforts to understand it, the molecular basis of GC regulated cell death and the resistance phenomenon remains, however, poorly understood. Using Affymetrix-based whole genome expression profiling our group has previously identified a number of prominent glucocorticoid-response genes [Blood 107 2061, 2006]. Promyelocytic leukemia zinc finger [PLZF] was one of the best candidate genes. This study was proposed to investigate the possible role of PLZF in GC regulated cell death in leukemic model cell line NALM6. To this end, we generated NALM6 cell line [bulk] transduced with a retroviral expression vectors, pHR-SFFV-PLZF-IRES-Puro [U426] and pHR-SFFV-Venus-IRES-Puro [U417], as control, for constitutive gene-expression. HEK293T cells were transfected transiently to generate viral particles. These cell lines were characterized by Western blotting and used to assay the effect of constitutive PLZF expression. In conclusion, we report that bona fide transcription repressor PLZF, which turned out as prominent GC-regulated gene both in vivo and in vitro situations was found to enhance the GC-induced cell death [basal] in leukemic model cell line NALM6 after 48 and 72h time points