Characterization of the bone marrow endosteal niche in JAK2-mutated myeloproliferative neoplasms

• Grant number: 17/15484-4
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): December 01, 2017
• Effective date (End): December 09, 2019
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Lorena Lôbo de Figueiredo Pontes
• Grantee: Talita Perez Sanches
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Myeloproliferative Neoplasms (MPN) originate from molecular abnormalities at the hematopoietic stem cell (HSC) level, but alterations of the bone marrow niche may also contribute to the functional regulation of the neoplastic stem cells and of the normal residual HSCs and, thus, collaborate to the pathophysiology of the disease. Therefore, considering that these diseases are not only dependent on oncogenic mutations, we aim to study the cellular components of the bone marrow microenvironment that may interact with HSCs and affect their function and transformation. We believe that MPN originate not only from intrinsic defects of HSCs, but also from its regulation by an abnormal niche, capable of sustaining the proliferative advantage of the myelopoiesis. Thus, we intend to characterize phenotypically and functionally the cells that support the hematopoietic niche located at the endosteum, comprised of endothelial cells, osteoblasts and mesenchymal stem cells, using a knockin transgenic murine model of conditional heterozygous expression of Jak2V617F. This work aims to bring new knowledge on the function of the niche cells in JAK2-associated MPN, and may contribute to elucidate the mechanisms by which they participate in the development and maintenance of the neoplastic myeloid proliferation at the expense of normal hematopoiesis. Finally, this investigation will possibly point out new therapeutic targets directed at the regulatory signals between HSCs and the bone marrow microenvironment. (AU)

Academic Publications

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

SANCHES, Talita Perez. Characterization of the endosteal niche in myeloproliferative neoplasms associated to the Jak2V617F mutation. 2020. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.