项目来源
巴西圣保罗研究基金(FAPESP)
项目主持人
Mariana Lazarini
项目受资助机构
Escola Paulista de Medicina.Universidade Federal de São Paulo.Campus São Paulo.São Paulo,SP,Brazil
立项年度
2025
立项时间
未公开
项目编号
24/09541-9
项目级别
国家级
研究期限
未知 / 未知
受资助金额
未知
学科
Health Sciences
学科代码
未公开
基金类别
Scholarships abroad-Research Internship-Doctorate(Direct)
关键词
Leucemia mieloide aguda ; Hematologia ; Reparo do DNA ; Proteínas rho de ligação ao GTP ; Adesão celular ; Genes p53 ; Dano ao DNA ;
参与者
Stephany Suelen de Castro Sampaio；Sandrine Etienne-Manneville
参与机构
Institut Pasteur,France
项目标书摘要：Proliferation and survival of immature hematopoietic stem cells rely on their bi-directional interactions with components of the bone marrow microenvironment.These interactions also occur in leukemia stem cells and are essential for leukemia development and therapy response.The Rho GTPase family of proteins plays a crucial role in regulating cellular adhesion and migration,through the regulation of cytoskeletal dynamics.However,the role of Rho GTPases has been poorly explored in leukemia.We hypothesize that RhoA or RhoC signaling are recruited in the communication between leukemia cells and the bone marrow microenvironment to regulate cell adhesion and migration.Therefore,our aim in this study is to evaluate the effects of RhoA or RhoC silencing on the adhesion and migration process of leukemia cells on different niche components(proteins and stromal cells).Cell adhesion and migration will be evaluated in vitro using time lapse microscopy with myeloid cell lines(U937 and OCI-AML3)stably silenced for RhoA or RhoC with lentivirus.HS-5 cell line will be used as a model of stromal cells.The elucidation of the specific contributions of RhoA and RhoC GTPases to leukemia cell adhesion and migration will contribute to understand the mechanism used by leukemia cells for survival and proliferation in the bone marrow microenvironment.The envisaged outcomes hold the potential to catalyze the development of innovative therapeutic avenues for leukemia targeting Rho GTPasesto enhance patient outcomes and well-being.
Application Abstract: Proliferation and survival of immature hematopoietic stem cells rely on their bi-directional interactions with components of the bone marrow microenvironment.These interactions also occur in leukemia stem cells and are essential for leukemia development and therapy response.The Rho GTPase family of proteins plays a crucial role in regulating cellular adhesion and migration,through the regulation of cytoskeletal dynamics.However,the role of Rho GTPases has been poorly explored in leukemia.We hypothesize that RhoA or RhoC signaling are recruited in the communication between leukemia cells and the bone marrow microenvironment to regulate cell adhesion and migration.Therefore,our aim in this study is to evaluate the effects of RhoA or RhoC silencing on the adhesion and migration process of leukemia cells on different niche components(proteins and stromal cells).Cell adhesion and migration will be evaluated in vitro using time lapse microscopy with myeloid cell lines(U937 and OCI-AML3)stably silenced for RhoA or RhoC with lentivirus.HS-5 cell line will be used as a model of stromal cells.The elucidation of the specific contributions of RhoA and RhoC GTPases to leukemia cell adhesion and migration will contribute to understand the mechanism used by leukemia cells for survival and proliferation in the bone marrow microenvironment.The envisaged outcomes hold the potential to catalyze the development of innovative therapeutic avenues for leukemia targeting Rho GTPasesto enhance patient outcomes and well-being.
