Science · 1997 · 794 citations · 22 references
Life SciencesMolecular BiologyOncologyCell SignalingCytogeneticsSignal TransductionCancer Cell SignalingCytokine Receptor SignalingGene Fusions In CancerOncogene ActivationOncogenic Fusion GenesReceptor Tyrosine Kinase SignalingEts Family OncogenesEts Family Transcription FactorsJak-stat Signaling PathwayJanus Kinase-stat Signaling ActivationOligomerizationOncogenic Fusion ProteinsReceptor Tyrosine Kinase ActivationReceptors
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.
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Inhibition of acute lymphoblastic leukaemia by a Jak-2 inhibitor
Naftaly Meydan, T Grunberger, Harjit Dadi et al. · Nature · 1996 · 912 citations
The t(12;21) of acute lymphoblastic leukemia results in a tel-AML1 gene fusion
M Mauchauffé, Maryvonne Le Coniat, Ilya Chumakov et al. · Blood · 1995 · 552 citations · Full text