We have recently reported inactivation of the tyrosine phosphatase PTPN2 (also known as TC-PTP) through deletion of the entire gene locus in about 6% of T-cell acute lymphoblastic leukemias (T-ALL). T-ALL is an aggressive disease of the thymocytes and characterized by the stepwise accumulation of chromosomal abnormalities and gene mutations. In this work we confirm the strong association of PTPN2 deletion with TLX1 and NUP214-ABL1 expression. In addition, we identify cooperation of PTPN2 deletion with activating JAK1 gene mutations. Activating mutations in the JAK1 kinase occur in about 10% of human T-ALL, and aberrant kinase activity has been shown to confer proliferation and survival advantages. Our current work shows that part of JAK1 mutation-positive T-ALL harbor deletions of the tyrosine phosphatase PTPN2, a known negative regulator of the JAK/STAT pathway. We provide evidence that downregulation of Ptpn2 sensitizes lymphoid cells to JAK1 mediated transformation and reduces their sensitivity to JAK inhibition.