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

doi:10.1126/science.278.5341.1309

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

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Résumé

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.

langue originale	Anglais
Pages (de - à)	1309-1312
Nombre de pages	4
journal	Science
Volume	278
Numéro de publication	5341
Les DOIs	https://doi.org/10.1126/science.278.5341.1309
état	Publié - 14 nov. 1997

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10.1126/science.278.5341.1309

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title = "A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia",

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.",

author = "Virginie Lacronique and Anthony Boureux and {Della Valle}, V{\'e}ronique and H{\'e}l{\`e}ne Poirel and {Tran Quang}, Christine and Martine Mauchauff{\'e} and Christian Berthou and Michel Lessard and Roland Berger and Jacques Ghysdael and Bernard, {Olivier A.}",

year = "1997",

month = nov,

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doi = "10.1126/science.278.5341.1309",

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T1 - A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia

AU - Lacronique, Virginie

AU - Boureux, Anthony

AU - Della Valle, Véronique

AU - Poirel, Hélène

AU - Tran Quang, Christine

AU - Mauchauffé, Martine

AU - Berthou, Christian

AU - Lessard, Michel

AU - Berger, Roland

AU - Ghysdael, Jacques

AU - Bernard, Olivier A.

PY - 1997/11/14

Y1 - 1997/11/14

N2 - 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.

AB - 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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