A TEL-JAK2 Fusion Protein with Constitutive Kinase Activity in Human Leukemia
Virginie Lacronique,
Anthony Boureux,
Véronique Della Valle,
Hélène Poirel,
Christine Tran Quang,
Martine Mauchauffé,
Christian Berthou,
Michel Lessard,
Roland Berger,
Jacques Ghysdael,
Olivier A. Bernard
*
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.
V. Lacronique, V. Della Valle, H. Poirel, M. Mauchauffé, R. Berger, O. A. Bernard, U 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.
A. Boureux, C. Tran Quang, J. Ghysdael, CNRS Unité Mixte de
Recherche 146, Institut Curie-Section de Recherche, Centre
Universitaire, 91405 Orsay Cedex, France.
C. Berthou and M. Lessard, Unité d'Hématologie,
Laboratoire de Cytogénétique, Hôpital Morvan, Centre
Hospitalier Régional de Brest, 29609 Brest Cedex, France.
*
To whom correspondence should be addressed.
