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A TEL-JAK2 Fusion Protein with Constitutive Kinase Activity in Human Leukemia

Science  14 Nov 1997:
Vol. 278, Issue 5341, pp. 1309-1312
DOI: 10.1126/science.278.5341.1309

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Abstract

The Janus family of tyrosine kinases (JAK) plays an essential role in development and in coupling cytokine receptors to downstream intracellular signaling events. A t(9;12)(p24;p13) chromosomal translocation in a T cell childhood acute lymphoblastic leukemia patient was characterized and shown to fuse the 3′ portion ofJAK2 to the 5′ region of TEL, a gene encoding a member of the ETS transcription factor family. The TEL-JAK2 fusion protein includes the catalytic domain of JAK2 and the TEL-specific oligomerization domain. TEL-induced oligomerization of TEL-JAK2 resulted in the constitutive activation of its tyrosine kinase activity and conferred cytokine-independent proliferation to the interleukin-3–dependent Ba/F3 hematopoietic cell line.

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