Muhammad WASIM, Muhammad MANSHA, Muhammad TAYYAB

PLZF overexpression in T-ALL cell line CEM-C7H2-2C8 downregulates glucocorticoid receptor (GR) and its target genes

Glucocorticoids (GCs) induce cell cycle arrest and apoptosis in lymphoid cells and constitute a central component in the treatment of lymphoid malignancies. The molecular basis of this clinically important phenomenon remains, however, poorly understood. Using whole genome expression profiling we have previously identified glucocorticoid response genes in children with acute lymphoblastic leukemia (ALL). The promyelocytic leukemia zinc finger (PLZF) appeared as one of the most promising candidate genes, which has been implicated in the pathogenesis of several leukemia types. We have already established that transgenic PLZF reduced the sensitivity to GC-induced apoptosis in the CEM-C7H2-2C8 leukemic cell line and knockdown of PLZF resulted in a small but significant increase in cell death in this cell line. The present study was proposed to find a plausible molecular explanation for this protective effect of PLZF against GC-induced cell death. It was found that doxycycline-regulated PLZF overexpression in the CCRF-CEM T-ALL cell line downregulates the GC-induced GR expression and its target genes, which resulted in reduced apoptosis induced by GC.

Anahtar Kelimeler:

PLZF, GR, glucocorticoid-response gene, glucocorticoid-induced apoptosis, leukemia cell line

PLZF overexpression in T-ALL cell line CEM-C7H2-2C8 downregulates glucocorticoid receptor (GR) and its target genes

Keywords:

PLZF, GR, glucocorticoid-response gene, glucocorticoid-induced apoptosis, leukemia cell line,

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