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

Beth A. Lubeck, Philip E. Lapinski, Jennifer A. Oliver, Olga Ksionda, Luis F. Parada, Yuan Zhu, Ivan Maillard, Mark Chiang, Jeroen Roose, Philip D. King

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Ras GTPase-activating proteins (RasGAPs) inhibit signal transduction initiated through the Ras small GTPbinding 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 doubledeficient 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.

Original languageEnglish (US)
Pages (from-to)31-35
Number of pages5
JournalJournal of Immunology
Volume195
Issue number1
DOIs
StatePublished - Jul 1 2015

Fingerprint

p120 GTPase Activating Protein
ras GTPase-Activating Proteins
Neurofibromin 1
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
T-Lymphocytes
Cell Lineage
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Signal Transduction

ASJC Scopus subject areas

  • Immunology

Cite this

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. / Lubeck, Beth A.; Lapinski, Philip E.; Oliver, Jennifer A.; Ksionda, Olga; Parada, Luis F.; Zhu, Yuan; Maillard, Ivan; Chiang, Mark; Roose, Jeroen; King, Philip D.

In: Journal of Immunology, Vol. 195, No. 1, 01.07.2015, p. 31-35.

Research output: Contribution to journalArticle

Lubeck, Beth A. ; Lapinski, Philip E. ; Oliver, Jennifer A. ; Ksionda, Olga ; Parada, Luis F. ; Zhu, Yuan ; Maillard, Ivan ; Chiang, Mark ; Roose, Jeroen ; King, Philip D. / 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. In: Journal of Immunology. 2015 ; Vol. 195, No. 1. pp. 31-35.
@article{8dcfc066f5924edca51d46111da4c75a,
title = "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",
abstract = "Ras GTPase-activating proteins (RasGAPs) inhibit signal transduction initiated through the Ras small GTPbinding 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 doubledeficient 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.",
author = "Lubeck, {Beth A.} and Lapinski, {Philip E.} and Oliver, {Jennifer A.} and Olga Ksionda and Parada, {Luis F.} and Yuan Zhu and Ivan Maillard and Mark Chiang and Jeroen Roose and King, {Philip D.}",
year = "2015",
month = "7",
day = "1",
doi = "10.4049/jimmunol.1402639",
language = "English (US)",
volume = "195",
pages = "31--35",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "1",

}

TY - JOUR

T1 - Cutting edge

T2 - 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

AU - Lubeck, Beth A.

AU - Lapinski, Philip E.

AU - Oliver, Jennifer A.

AU - Ksionda, Olga

AU - Parada, Luis F.

AU - Zhu, Yuan

AU - Maillard, Ivan

AU - Chiang, Mark

AU - Roose, Jeroen

AU - King, Philip D.

PY - 2015/7/1

Y1 - 2015/7/1

N2 - Ras GTPase-activating proteins (RasGAPs) inhibit signal transduction initiated through the Ras small GTPbinding 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 doubledeficient 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.

AB - Ras GTPase-activating proteins (RasGAPs) inhibit signal transduction initiated through the Ras small GTPbinding 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 doubledeficient 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.

UR - http://www.scopus.com/inward/record.url?scp=84932118007&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84932118007&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1402639

DO - 10.4049/jimmunol.1402639

M3 - Article

C2 - 26002977

AN - SCOPUS:84932118007

VL - 195

SP - 31

EP - 35

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 1

ER -