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Identification of chromosomal abnormalities in patients with Myelodysplastic Syndromes and correlation with the methylation profile and expression of genes IRF-1 and PPARgamma

Grant number: 12/10381-9
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): August 01, 2012
Effective date (End): September 30, 2014
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Maria de Lourdes Lopes Ferrari Chauffaille
Grantee:Silvia Natsuko Akutsu
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated scholarship(s):13/13312-0 - Analysis of chromosomal instability through the cytokinesesis-block micronucleous assay (CBMN) in myelodysplastic syndromes, BE.EP.MS


Background: The Myelodysplastic Syndromes are a group of clonal disorders of hematopoiesis characterized by inefficient hematopoiesis, peripheral blood cytopenias, dysplasia hematopoietic in one or more cell of the myeloid lineage, and increased risk of progression to acute myeloid leukemia (LMA). The clinical phenotype of patients with MDS are diverse with respect to the number and severity of cytopenias, cellularity and blast count in the bone marrow, rate of survival, and response to treatment. The clinical heterogeneity of MDS is reflection of the various pathogenic mechanisms responsible for their development. Knowleadge of the molecular pathogenesis of MDS is still limited. Autoimmune phenomena have been reported in about 10% of patients with MDS. Althought the pathological basis for the occurrence of autoimmune diseases in patients with MDS is not completely understood, several studies have shown abnormal immune function in MDS. A variety of immunologic abnormalities have been described in SMDs both humoral and cellular level. Objective: This study proposes the investigation of two genes that may be involved in the pathophysiology of immunological events related to SMDs, which are, IRF-1 (Interferon Regulatory Factor-1) and PPARg (Activated Receptor Gamma peroxisome proliferators).Materials and methods: Samples will be collected from peripheral blood of 40 MDS patients and controls to be assessed the methylation profile and expression of genes IRF-1 and PPARg, relating them with chromosomal abnormalities detected by karyotyping and FISH.

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