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Title: Mutation of the receptor tyrosine phosphatase PTPRC (CD45) in T-cell acute lymphoblastic leukemia
Authors: Porcu, MichaĆ«l
Kleppe, Maria
Gianfelici, Valentina
Geerdens, Ellen
De Keersmaecker, Kim
Tartaglia, Marco
Foà, Robin
Soulier, Jean
Cauwelier, Barbara
Uyttebroeck, Anne
Macintyre, Elizabeth
Vandenberghe, Peter
Asnafi, Vahid
Cools, Jan # ×
Issue Date: May-2012
Publisher: W.B. Saunders
Series Title: Blood vol:119 issue:19 pages:4476-4479
Abstract: The protein tyrosine phosphatase CD45, encoded by the PTPRC gene, is well known as a regulator of B- and T-cell receptor signaling. In addition, CD45 negatively regulates JAK family kinases downstream of cytokine receptors. Here, we report the presence of CD45 inactivating mutations in T-cell acute lymphoblastic leukemia. Loss-of-function mutations of CD45 were detected in combination with activating mutations in IL-7R, JAK1, or LCK, and down-regulation of CD45 expression caused increased signaling downstream of these oncoproteins. Furthermore, we demonstrate that down-regulation of CD45 expression sensitizes T cells to cytokine stimulation, as observed by increased JAK/STAT signaling, whereas overexpression of CD45 decreases cytokine-induced signaling. Taken together, our data identify a tumor suppressor role for CD45 in T-cell acute lymphoblastic leukemia.
URI: 
ISSN: 0006-4971
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Laboratory of Molecular Biology of Leukemia
Laboratory for Genetics of Malignant Disorders
× corresponding author
# (joint) last author

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