Bone marrow mesenchymal stromal cells deregulation effect on BCR-ABL1-Myeloprolife...
| Grant number: | 18/01756-5 |
| Support type: | Scholarships in Brazil - Post-Doctorate |
| Effective date (Start): | December 01, 2018 |
| Effective date (End): | November 30, 2021 |
| Field of knowledge: | Health Sciences - Medicine |
| Principal Investigator: | Fabíola Attié de Castro |
| Grantee: | Maira da Costa Cacemiro |
| Home Institution: | Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil |
Abstract Myeloproliferative neoplasms (MPN) are hematological disorders characterized by increased cell proliferation and accumulation of mature and precursor myeloid cells in peripheral blood independently of cytokine stimuli and growth factors.The discovery of genetic mutations since 2005 has contributed to the elucidation of the physiopathology of MPN. However, despite the knowledge accumulated in the last decade, there is still a need to elucidate the cellular and molecular mechanisms that contribute to the appearance and progression of this group of diseases, including alterations of the hematopoietic niche.Although dysregulated hematopoiesis present in MPN is mainly attributed to molecular changes in the hematopoietic stem cell (HSC), the abnormality of the medullary microenvironment seems to be important in the development of these diseases. The stromal microenvironment of the bone marrow is composed of extracellular matrix and specialized cells, with emphasis on the mesenchymal stromal cells (MSC) that guarantee the maintenance of the potential for self-renewal and pool of HTC. MSC contribute to the quiescence of HSC, protecting them from pro-apoptotic stimuli and differentiation. In addition to genetic alterations in HSC and changes in the microenvironment, it is also considered that MPN are onco-inflammatory diseases and are characterized by abnormal activity of the immune system.Therefore, our hypothesis is that alterations in the immunomodulatory profile of MSC, as well as structural or expression changes of components of the hematopoietic marrow niche contribute to the physiopathology of MPN. We believe that MSC can modulate the hematopoietic niche by means of cytokines, lipid mediators and growth factors, capable of altering the functioning and structure of the medullary microenvironment, favoring the neo-angiogenesis and proliferation of neoplastic myeloid cells.The present project will evaluate the immunomodulatory potential of the multipotent mesenchymal stromal cells of MPN aiming to establish the relationship between the alteration of the hematopoietic microenvironment and the physiopathology of MPN. | |