| Grant number: | 11/20135-2 |
| Support Opportunities: | Regular Research Grants |
| Start date: | March 01, 2012 |
| End date: | April 30, 2014 |
| Field of knowledge: | Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology |
| Principal Investigator: | Fabíola Attié de Castro |
| Grantee: | Fabíola Attié de Castro |
| Host Institution: | Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil |
| City of the host institution: | Ribeirão Preto |
Abstract
Polycythemia Vera (PV), Essential Thrombocytosis (ET), and Primary Myelofibrosis (PMF) are Ph-negative chronic myeloproliferative neoplasms characterized by the either the presence of progenitors independence or by hypersensitive to numerous cytokines associated with cell differentiation and intense proliferation. The cellular and molecular mechanisms involved in the pathogenesis and progression of these neoplasms have not been fully elucidated and therefore only a few diagnostic and prognostic markers have been described. The contribution of the V617F JAK mutation to the clinical laboratory features of PV has been described, however this mutation partly explains the myeloproliferation and myeloaccumulation verified both in ET and PMF. Since only about 50% of ET and PMF patients present the JAK2 V617F mutation, we hypothesize that cell proliferation and apoptosis deregulation, mutations in the MPL gene TET2 and epigenetic abnormalities also contribute to the pathogenesis of these diseases. The present project aims to describe potential alterations in the molecules involved in regulation of apoptosis and cell cycle control, in the JAK/STAT pathway and methylation profile, mainly in V617F JAK2 negative patients. Specifically this study aims to evaluate in PV, ET and PMF: 1) the protein expression using reverse protein arrays; 2) the methylation profile of genes related to apoptosis and cell cycle (qPCR Array System); 3) the presence of MPL and JAK2 (12 of 14 exon) mutations. Another experimental approach constitutes to verify if constitutive kinase activity of JAK2 induces epigenetic alterations in genes relates to apoptosis and cell cycle. In this case, this cell lineage will be treated either with the inhibitor, or with classic apoptogenic agents that act in the TRAIL death receptor pathway, and treated cells will be evaluated for their susceptibility to apoptosis, and the patterns of protein expression and epigenetic profile. Overall, this study will provide a description of new therapeutic targets and the role of epigenetic and molecular alterations in the pathogenesis of these diseases in patients positive and negative for JAK2 mutation. (AU)
| Articles published in Agência FAPESP Newsletter about the research grant: |
| More itemsLess items |
| TITULO |
| Articles published in other media outlets ( ): |
| More itemsLess items |
| VEICULO: TITULO (DATA) |
| VEICULO: TITULO (DATA) |