Cutting Edge: Codeletion of the Ras GTPase-Activating Proteins (RasGAPs) Neurofibromin 1 and p120 RasGAP in T Cells Results in the Development of T Cell Acute Lymphoblastic Leukemia
Year: 2015
Type: article
Abstract: Ras GTPase-activating proteins (RasGAPs) inhibit signal transduction initiated through the Ras small GTP-binding protein. However, which members of the RasGAP family act as negative regulators of T cell responses is not completely understood. In this study, we investigated potential roles for the RasGAPs RASA1 and neurofibromin 1 (NF1) in T cells through the generation and analysis of T cell-specific RASA1 and NF1 double-deficient mice. In contrast to mice lacking either RasGAP alone in T cells, double-deficient mice developed T cell acute lymphoblastic leukemia/lymphoma, which originated at an early point in T cell development and was dependent on activating mutations in the Notch1 gene. These findings highlight RASA1 and NF1 as cotumor suppressors in the T cell lineage.
Source: The Journal of Immunology
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Research Training in Experimental Immunology, G109073144, G1404790370, RASA1-mediated control of lymphatic vessel growth and function, G4219210399, Molecular understanding of leukemic bone marrow cytokine-Ras signals and metabolic dependence, G491642029, G4933786434, University of Michigan Rogel Cancer Center Support Grant 2023-2028
OpenAlex ID: W1678308122