Role of DAMPs released during tumor lysis process in the modulation of apoptosis and proliferation in acute myeloid leukemia cells

• Grant number: 16/06908-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2016
• End date: December 31, 2016
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Welbert de Oliveira Pereira
• Grantee: Évelyn Helena Ascendino da Mata
• Host Institution: Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEPAE). Sociedade Beneficente Israelita Brasileira Albert Einstein (SBIBAE). São Paulo , SP, Brazil

Abstract

Acute Myeloid Leukemia (AML) is characterized by uncontrolled proliferation of myeloid hematopoietic progenitors, compromising the hematopoiesis and leading to dysfunction of multiple organs. A massive cell necrosis is induced by chemotherapeutics action and this allows the release of Danger Associated Molecular Patterns (DAMPs). These molecules stimulates Toll like receptors (TLRs), activating pathways involved in modulating cell proliferation and apoptosis. The Project is based in the hypothesis that the tumoral lysis phenomenon, frequent in AML, constitutes a source of DAMPs which potentially stimulates the TLRs of the non-lysed leukemia cells, possibly tampering with the neoplasia development. Cell lines from the AML patients will be used and submited to a model in tumoral lysis in vitro. After the interaction of necrotic cells with viable leukemia cells, the downstream pathways derived of the activation of TLRs will be studied, as well as the signalling impact in the regulation of the cell proliferation and resistance to apoptosis. (AU)