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PubMed · 10845925

TEL-JAK2 transgenic mice develop T-cell leukemia.

C Carron·F Cormier·A Janin·V Lacronique·M Giovannini·M T Daniel·O Bernard·J Ghysdael
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Abstract

We previously reported a fusion between TEL and JAK2 in a t(9;12)(p24;p13) chromosomal translocation in childhood acute T-cell leukemia. This fusion gene encodes a TEL-JAK2 chimeric protein in which the 336 amino-terminal residues of TEL, including its specific self-association domain, are fused to the kinase domain of JAK2. TEL-JAK2 exhibits constitutive activation of its tyrosine kinase activity which, in turn, confers growth factor-independent proliferation to the interleukin-3-dependent Ba/F3 hematopoietic cell line. To elucidate the properties of TEL-JAK2 in primary cells and to create an animal model for TEL-JAK2-induced leukemia, we generated transgenic mice in which the TEL-JAK2 complementary DNA was placed under the transcriptional control of the EmuSRalpha enhancer/promoter. TEL-JAK2 founder mice and their transgenic progeny developed fatal leukemia at 4 to 22 weeks of age. Selective amplification of CD8-positive T cells was observed in blood, lymph nodes, thymus, spleen, and bone marrow. Expression of a tyrosine-phosphorylated TEL-JAK2 protein and activation of STAT1 and STAT5 (signal transducer and activator of transcription) were detected in leukemic tissues. TEL-JAK2 diseased mice also displayed invasion of nonhematopoietic organs, including liver, brain, lung, and kidney, by leukemic T cells. Leukemic organs of founder and transgenic progeny contained a monoclonal/oligoclonal T-cell population as analyzed by the rearrangement of the TCRbeta locus. Transplantation of TEL-JAK2 leukemic cells in nude mice confirmed their invasive nature. We conclude that the TEL-JAK2 fusion is an oncogene in vivo and that its expression in lymphoid cells results in the preferential expansion of CD8-positive T cells. (Blood. 2000;95:3891-3899)

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AnimalsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesDNA, ComplementaryEnhancer Elements, GeneticHumansLeukemia, T-CellLeukocyte CountMiceMice, TransgenicOncogene Proteins, FusionPromoter Regions, GeneticSpleenT-LymphocytesThymus GlandTranscription, GeneticJanus Kinase 2ETS Translocation Variant 6 ProteinJournal ArticleResearch Support, Non-U.S. Gov't

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C Carron, F Cormier, A Janin, V Lacronique, M Giovannini, M T Daniel, O Bernard, J Ghysdael. 2000-06-15. TEL-JAK2 transgenic mice develop T-cell leukemia.. https://pubmed.ncbi.nlm.nih.gov/10845925/

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