Mutation of the receptor tyrosine phosphatase PTPRC (CD45) in T-cell acute lymphoblastic leukemia

Michaël Porcu, Maria Kleppe, Valentina Gianfelici, Ellen Geerdens, Kim De Keersmaecker, Marco Tartaglia, Robin Foà, Jean Soulier, Barbara Cauwelier, Anne Uyttebroeck, Elizabeth MacIntyre, Peter Vandenberghe, Vahid Asnafi, Jan Cools

Research output: Contribution to journalArticlepeer-review

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 downregulation of CD45 expression sensitizes T cells to cytokine stimulation, as observed by increased JAK/STAT signaling, whereas overexpression ofCD45decreases cytokineinduced signaling. Taken together, our data identify a tumor suppressor role for CD45 in T-cell acute lymphoblastic leukemia.

Original languageEnglish
Pages (from-to)4476-4479
Number of pages4
JournalBlood
Volume119
Issue number19
DOIs
Publication statusPublished - May 10 2012

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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