DNMT3A mutations, expression and function in myelodysplasic syndromes and acute myeloid leukemia.

• Grant number: 11/15905-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2012
• End date: February 28, 2014
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Fabíola Traina
• Grantee: Renata Scopim Ribeiro
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

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.

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)

SCOPIM-RIBEIRO, RENATA; MACHADO-NETO, JOAO AGOSTINHO; CAMPOS, PAULA DE MELO; NIEMANN, FERNANDA SOARES; LORAND-METZE, IRENE; COSTA, FERNANDO FERREIRA; OLALLA SAAD, SARA TERESINHA; TRAINA, FABIOLA. Low Ten-eleven-translocation 2 (TET2) transcript level is independent of TET2 mutation in patients with myeloid neoplasms. DIAGNOSTIC PATHOLOGY, v. 11, MAR 16 2016. (11/51959-0, 12/09982-8, 11/15905-3)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

RIBEIRO, Renata Scopim. Investigation of TET2 and DNMT3A expression in myelodysplastic syndrome and acute myeloid leukemia. 2014. Master's Dissertation - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas Campinas, SP.