Effects of inhibition of HDAC9 gene in acute lymphocytic leukemia

Abstract

Acute Lymphoblastic Leukemia (ALL) is the most common hematologic malignancy in childhood. It's a heterogeneous disease and despite advances in treatment approximately 20% of patients have relapse or death indicating the need for differentiated therapies for this group. The analysis of genetic and epigenetic abnormalities may enable a more accurate diagnosis and the development of specific molecular therapies. Recently, epigenetic drugs as histone deacetylasesinhibitors (HDACis) have shown promising effects in several types of cancer, and a study realized by our group showed that the expression of some HDACs genes is associated with clinical and biological characteristics of patients with ALL. Among the most important results was observed that the HDAC9 gene overexpression is associated with poor prognosis and shorter survival, however the reasons for this relationship are not clear. Considering the results obtained in the cited work, this study will evaluate the effects of inhibition of the HDAC9 gene using small interference RNA (siRNA) combined or not with HDACis ALL cell lines. To confirm the inhibition of HDAC9 gene and protein after treatment with siRNA and iHDAC, real-time PCR and western blot techniques respectively will be perform. The effects of inhibition of the HDAC9gene will be evaluated by functional assays of cell proliferation, apoptosis and cell cycle in ALL cell lines.