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Deletion of the protein tyrosine phosphatase gene PTPN2 in T-cell acute lymphoblastic leukemia

Open access
Kleppe, Maria, Lahortiga, Idoya, El Chaar, Tiama, De Keersmaecker, Kim, Mentens, Nicole, Graux, Carlos, Van Roosbroeck, Katrien, Ferrando, Adolfo A, Langerak, Anton W, Meijerink, Jules P P, Sigaux, François, Haferlach, Torsten, Wlodarska, Iwona, Vandenberghe, Peter, Soulier, Jean, Cools, Jan·2010·Nature Genetics

Abstract

PTPN2 (protein tyrosine phosphatase non-receptor type 2, also known as TC-PTP) is a cytosolic tyrosine phosphatase that functions as a negative regulator of a variety of tyrosine kinases and other signaling proteins. In agreement with its role in the regulation of the immune system, PTPN2 was identified as a susceptibility locus for autoimmune diseases. In this work, we describe the identification of focal deletions of PTPN2 in human T-cell acute lymphoblastic leukemia (T-ALL). Deletion of PTPN2 was specifically found in T-ALLs with aberrant expression of the TLX1 transcription factor oncogene, including four cases also expressing the NUP214-ABL1 tyrosine kinase. Knockdown of PTPN2 increased the proliferation and cytokine sensitivity of T-ALL cells. In addition, PTPN2 was identified as a negative regulator of NUP214-ABL1 kinase activity. Our study provides genetic and functional evidence for a tumor suppressor role of PTPN2 and suggests that expression of PTPN2 may modulate response to treatment.

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Metadata

Authors
Kleppe, M., Lahortiga, I., El Chaar, T., De Keersmaecker, K., Mentens, N., Graux, C., Van Roosbroeck, K., Ferrando, A. A., Langerak, A. W., Meijerink, J. P. P., Sigaux, F., Haferlach, T., Wlodarska, I., Vandenberghe, P., Soulier, J., & Cools, J.
Venue
Nature Genetics
Published
2010-05-16
Volume
42
Issue
6
Pages
530-535
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
OpenAlex
W2002379520
Cited by
198
References
4
FWCI
6.62
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Deletion of the protein tyrosine phosphatase gene PTPN2 in T-cell acute lymphoblastic leukemia. https://app.cochat.ai/papers/10.1038/ng.587
The paper
Kleppe, M., Lahortiga, I., El Chaar, T., De Keersmaecker, K., Mentens, N., Graux, C., Van Roosbroeck, K., Ferrando, A. A., Langerak, A. W., Meijerink, J. P. P., Sigaux, F., Haferlach, T., Wlodarska, I., Vandenberghe, P., Soulier, J., & Cools, J. (2010). Deletion of the protein tyrosine phosphatase gene PTPN2 in T-cell acute lymphoblastic leukemia. Nature Genetics. https://doi.org/10.1038/ng.587

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.