|Support type:||Scholarships in Brazil - Master|
|Effective date (Start):||March 01, 2012|
|Effective date (End):||February 28, 2014|
|Field of knowledge:||Health Sciences - Medicine - Medical Clinics|
|Principal Investigator:||Fabíola Traina|
|Grantee:||Renata Scopim Ribeiro|
|Home Institution:||Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil|
Genomic sequencing in patients with myeloid malignancies resulted in the identification of several new recurrent mutations. Mutations in genes involved in epigenetic regulation, such as TET2, IDH1, IDH2 and DNMT3A has been recently described in patients with myeloid malignancies including myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) and myeloproliferative diseases (MPD). Some mutations results in clinical implications, however, the functional role of these protein and their role in the leukemogenesis has not been fully elucidated. The aim of the present study is to investigate DNMT3A mutation and expression in MDS and AML and also the phenotypic consequence of DNMT3A silencing in AML cell lines. DNA and RNA samples from patients with MDS and AML will be submitted to PCR and sequencing, quantitative PCR and Western Blotting. LMA cell lines will be submitted to DNMT3A silencing using lentivirus, and functional studies to evaluate proliferation and apoptosis will be performed. The PI3K/AKT/mTOR signaling will be evaluated through western blotting. The study of the functional consequence of DNMT3A silencing may help in the better understanding of how DNMT3A and its mutation participate in the leukemogenesis. The findings in the cell line models will be applied to the patient samples with DNMT3A mutation and reduced expression.