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J Immunol. 2015 Jul 1;195(1):31-5. doi: 10.4049/jimmunol.1402639. Epub 2015 May 22.

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.

Author information

1
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109;
2
Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143;
3
Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390;
4
Division of Molecular Medicine and Genetics, University of Michigan Medical School, Ann Arbor, MI 48109; and.
5
Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109.
6
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109; kingp@umich.edu.

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.

PMID:
26002977
PMCID:
PMC4475412
DOI:
10.4049/jimmunol.1402639
[Indexed for MEDLINE]
Free PMC Article

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