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A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia
V Lacronique1, A Boureux, V D Valle
1U 301 de l'Institut National de la Santé et de la Recherche Médicale and SD 401 No. 301 CNRS, Institut de Génétique Moléculaire, 27 rue Juliette Dodu, 75010 Paris, France.
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 of JAK2 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.