A TEL-JAK2 FUSION PROTEIN WITH CONSTITUTIVE KINASE-ACTIVITY IN HUMAN LEUKEMIA

The Janus family of tyrosine kinases (JAK) plays an essential role in development and in coupling cytokine receptors to downstream intracell ular signaling events. A t(9;12)(p24;p13) chromosomal translocation in a T cell childhood acute lymphoblastic leukemia patient was character ized 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 TE L-JAK2 resulted in the constitutive activation of its tyrosine kinase activity and conferred cytokine-independent proliferation to the inter leukin-3-dependent Ba/F3 hematopoietic cell line.