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

• Published in: Science (American Association for the Advancement of Science) Vol. 278; no. 5341; pp. 1309 - 1312
• Main Authors: Lacronique, Virginie, Boureux, Anthony, Della Valle, Véronique, Poirel, Helene, Quang, Christine Tran, Mauchauffé, Martine, Berthou, Christian, Lessard, Michel, Berger, Roland, Ghysdael, Jacques, Bernard, Olivier A.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 14.11.1997; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Amino Acid Sequence; Amino acids; Analysis; Animals; Base Sequence; Biological and medical sciences; Biopolymers; Cell Division; Cell growth; Cell Line; Cell lines; Cellular biology; Child, Preschool; Chromosomes; Complementary DNA; DNA; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Enzyme Activation; ETS Translocation Variant 6 Protein; Genomics; Hematologic and hematopoietic diseases; Humans; Interleukin-3 - physiology; Janus Kinase 2; Leukemia; Leukemia research; Leukemia-Lymphoma, Adult T-Cell - genetics; Leukemia-Lymphoma, Adult T-Cell - metabolism; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical research; Medical sciences; Mice; Milk Proteins; Molecular Sequence Data; Oncogene Proteins, Fusion - chemistry; Oncogene Proteins, Fusion - genetics; Oncogene Proteins, Fusion - metabolism; Phosphorylation; Protein tyrosine kinase; Protein-Tyrosine Kinases - chemistry; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; Proteins; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-ets; Repressor Proteins; Signal Transduction; STAT5 Transcription Factor; T lymphocytes; Trans-Activators - metabolism; Transcription Factors - chemistry; Transcription Factors - genetics; Transcription Factors - metabolism; Transcripts (Written Records); Transfection; Translocation (Genetics); Translocation, Genetic; Translocations (Genetics); Chromosomal aberration; Human; Cell proliferation; Breakpoint; Enzyme; Transferases; Acute; Malignant hemopathy; Enzymatic activity; Lymphoproliferative syndrome; T-Lymphocyte; Abnormal chromosome; Genetics; Acute lymphocytic leukemia; Fusion protein; Protein-tyrosine kinase; Hybrid gene; Chromosome translocation
• DOI: 10.1126/science.278.5341.1309
• ISSN: 0036-8075

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.