Investigation of the role of SEMA3A and VEGFA in myelodysplasia and acute leukemia deregulated pathways

• Grant number: 12/00529-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2012
• End date: February 29, 2016
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Sara Teresinha Olalla Saad
• Grantee: Bruna Palodetto
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Myelodysplastic syndromes (MDS)are a heterogeneous group of clonal hematopoietic disorders that display ineffective hematopoiesis. About a third of patients with MDS progress to AML. The microenvironment contributes to the regulation of self-renewal, maintenance, differentiation, proliferation and apoptosis of progenitor cells and when is abnormal can favor diseases development. Previous microarrayresults in our research group identified several transcripts with differential expression in CD34 + and stromal cells in bone marrow patientswith myelodysplasia. Among them, the VEGF is highly into CD34 + and SEMA3A in the stroma of these patients. The VEGF gene encodes the vascular endothelial growth factor (VEGF), it is known that this factor is secreted by a variety of malignancies, contributes to neoangiogenesis and is increased in AML and MDS patients. SEMA3A gene encodes Semaphorin Class 3, which is involved in vascularization, angiogenesis and tumor progression. As the VEGF factor has been previously related to neoangiogenesis and his receptor is NRP1 and SEMA3A is related to tumor progression and uses the same receptor, it is possible that SEMA3A inhibits the angiogenic effect by competing for the same VEGF receptor. The study of deregulated transcripts is important for understanding the transcriptional regulation and molecular mechanism related to the heterogeneity of hematological disorders. Since little is known about the role of VEGF and SEMA3A genes and their interaction in hematological diseases the aim of this study is to investigate the VEGF and SEMA3A function in deregulated pathways in MDS and acute leukemias.

Academic Publications

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

PALODETTO, Bruna. Influence of VEGFA and SEMA3A in the pathogenesis of myelodysplastic syndromes and acute leukemias. 2016. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas Campinas, SP.