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A transgenic mouse model for TEL-JAK2-induced B-cell lymphoma/leukemia

Leukemia volume 20, pages 182–185 (2006)Cite this article

The JAK-STAT pathway is a central mediator of cytokine signaling in hematopoietic cells, and its deregulation has been observed in human hematological and solid malignancies. The notion that JAK-STAT signaling may drive tumor formation has been strengthened by the identification of JAK2 genetic alterations in human leukemia. Initially, we and others have identified fusions of the JAK2 gene with the TEL(ETV6) gene in cases of human childhood T-cell acute lymphoblastic leukemia (ALL), pre-B ALL and atypical chronic myeloid leukemia (CML).1, 2 More recently, JAK2 fusions with the PCM1 and BCR genes have also been identified in CML and pre-B ALL.3, 4 In addition, a frequent JAK2 point mutation (JAK2V617F) has been identified in human clonal myeloproliferative disorders.5 Both the TEL-JAK2 fusion and the JAK2V617F mutation result in constitutive JAK2 tyrosine kinase activity.1, 5

Two different approaches have been pursued to model TEL-JAK2-induced leukemia in mice. Transgenic TEL-JAK2 expression driven by the EμSRα promoter/enhancer, which leads to B and T lymphoid-specific expression, resulted in highly penetrant oligoclonal T-cell leukemia/lymphoma in mice.6 Likewise, TEL-JAK2 retroviral transduction of bone marrow cells followed by adoptive transfer into irradiated mice induced a fatal mixed myeloproliferative and T-cell lymphoproliferative disorder.7 Unexpectedly, although both the TEL-JAK2 and PCM1-JAK2 fusions have been observed in human B-cell leukemia/lymphoma, none of the TEL-JAK2 mouse models developed B-cell malignancies.

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Acknowledgements

We thank Maryvonne Williame for excellent technical assistance, Françoise Cormier for animal expertise and the lab members for helpful discussions. This work was supported by a Marie Curie Fellowship of the European Community program ‘Improving the Human Research Potential and the Socio-Economic knowledge base’ (Contract No. HPMF-CT-2000-00481) (NRdS) and funds from the Centre National de la Recherche Scientifique (CNRS), Institut Curie, Section Recherche, the Association for International Cancer Research (AICR) and the Ligue Nationale contre le Cancer (Équipe labelisée la Ligue).

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  1. Institut Curie, CNRS UMR 146, Centre Universitaire, Bât. 110, Orsay, 91405, France

    N R dos Santos & J Ghysdael

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Santos, N., Ghysdael, J. A transgenic mouse model for TEL-JAK2-induced B-cell lymphoma/leukemia. Leukemia 20, 182–185 (2006). https://doi.org/10.1038/sj.leu.2404026

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