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

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Porcu, M. | Kleppe, M. | Gianfelici, V. | Geerdens, E. | Keersmaecker K., De | Tartaglia, M. | Foa, R. | Soulier, J. | Cauwelier, B. | Uyttebroeck, A. | Macintyre, E. | Vandeberghe, P. | Asnafi, V. | Cools, J.

Edité par CCSD ; American Society of Hematology -

International audience. 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 of CD45 decreases cytokine-induced signaling. Taken together, our data identify a tumor suppressor role for CD45 in T-cell acute lymphoblastic leukemia.

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