Effects of inhibition of HDAC9 gene in acute lymphocytic leukemia

• Grant number: 12/18383-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2013
• End date: May 31, 2016
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Luiz Gonzaga Tone
• Grantee: Daniel Antunes Moreno
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

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.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MORENO, DANIEL ANTUNES; RIBEIRO JUNIOR, HOWARD LOPES; ALBERTONI LARANJEIRA, ANGELO BRUNELLI; VEIGA CRUZEIRO, GUSTAVO ALENCASTRO; BORGES, KLEITON SILVA; SALOMAO, KARINA BEZERRA; RAMALHO, FERNANDO SILVA; YUNES, JOSE ANDRES; ARAUJO SILVA, CLEIDE LUCIA; REGO, EDUARDO MAGALHAES; et al. Panobinostat (LBH589) increase survival in adult xenografic model of acute lymphoblastic leukemia with t(4;11) but promotes antagonistic effects in combination with MTX and 6MP. MEDICAL ONCOLOGY, v. 39, n. 12, p. 10-pg., 2022-09-29. (12/18383-0)