Mutation of the receptor tyrosine phosphatase PTPRC (CD45) in T-cell acute lymphoblastic leukemia
Menée in vitro, cette étude met en évidence le rôle de suppresseur de tumeurs joué par CD45, une protéine à activité tyrosine-phosphatase codée par le gène PTPRC, dans la leucémie aiguë lymphoblastique T
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 (T-ALL). Loss-of-function mutations of CD45 were detected in combination with activating mutations in IL7R, JAK1 or LCK, and downregulation 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-ALL.