Abstract
The present project aims at investigating the factors involved in the self-renewal and maintenance of bone marrow neoplastic cells, as occurs in myelodysplasia, acute leukemias, and multiple myeloma. The common aspect between them all is that they all occur in high frequency in the population, and despite the considerable therapeutic advances achieved during the last decade, still have a poor prognosis. Therefore, complete remission of acute leukemia in adults is below 50%, and those who are not cured during the first year, rapidly succumb to the disease. In multiple myeloma and myelodysplasias, complete remission occurs in the minority of the cases and the only potentially curative option is allogeneic bone marrow transplantation Another important aspect of these disorders is that they are all related to the reciprocal interaction between the neoplastic cell and the microenvironment of the bone marrow, which regulate differentiation, proliferation, and the survival of neoplastic cells. In this project, the focus will be maintained upon the molecular mechanisms of these interactions, the study of epigenetic changes, and functional characterization of novel proteins involved in the pathogenesis of these disorders. For this purpose, we will investigate the aspects of the bone marrow niche which can facilitate the self-renewal of neoplastic cells, as well as the immunomodulatory effect of the bone marrow stroma upon the development of neoplasias and the autophagy process. Furthermore, we will continue the characterization of novel proteins previously described by our group and in full development such as ARHGAP21 and ANKHD1, and any other candidates which by chance may be discovered throughout the project, as a result from the latest generation of sequencing of specific cases We will also continue with the investigation of coding and non-coding transcripts, deregulated in the stroma and CD34+ cells of myelodysplasia patients, as published by our group. Novel drugs which are still being developed and patented by groups from UNICAMP or other groups, will also be an object of study. (AU)
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