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Gain of function in Jak2V617F-positive T-cells

Leukemia volume 31, pages 1000–1003 (2017)Cite this article

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Myeloproliferative neoplasms (MPNs) are clonal disorders of aging hematopoietic stem cells and early myeloid progenitors. A somatic activating point mutation in the Jak2 tyrosine kinase (Jak2V617F) is the most prevalent genetic aberration in BCR-ABL-negative MPNs. Janus kinases (JAKs) are essential for cytokine-induced intracellular signaling and their inactivation leads to impaired immune cell function. Therapeutic inhibition of JAKs in MPN patients causes decreased number and function of immune cells,1, 2 and therefore may contribute to increased incidence and re-activation of viral infections.3 Jak2V617F mutation is detectable in hematopoietic stem and progenitor cells of MPN patients and has also been described in lymphoid progenitors and more differentiated lymphocytes,4, 5, 6, 7 including Jak2V617F mutated T-cells.4 However, depending on the allelic burden, incidence and clone size, the number of Jak2V617F mutated T-cells may have been underestimated, and it is currently unclear whether both CD4+ and CD8+ T-lymphocytes may be equally affected by the Jak2V617F mutation.

Therefore, we aimed to assess for the frequency of Jak2V617F mutation in CD3+ T-lymphocytes of patients with high-allelic-burden MPNs and investigated the impact of Jak2V617F mutation on T-cell function in vivo. A model with T-cell-specific Jak2V617F expression was analyzed under physiological conditions and upon infection with an intracellular pathogen.

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Acknowledgements

We thank A Fenske (DVM) Otto-von-Guericke University) for his support with animal care and Dr R Hartig (Institute for Clinical and Molecular Immunology; Otto-von-Guericke University) for his support with cell sorting. This work was supported by the DFG-Collaborative Research Center (CRC854) to DS (Project A05) and TF and FHH (Project A20). All human samples were collected and stored in the Hematology Tissue-Bank Magdeburg (HTM) supported by the Jose-Carreras Foundation (SP12/04) to FHH; FHH was supported by the RegenerAging Initiative, Thuringia. This work was supported by the Deutsche Forschungsgemeinschaft Collaborative Research Center 854 (project A05 to DS, project A20 to TF and FH), the Jose-Carreras Foundation (SP12/04 to FHH) and the RegenerAging Initiative, Thuringia (FHH).

Author contributions

GN, CF, DW, TMS, FP and SJ conducted the experiments and analyzed the data. AM, TF and FHH provided the experimental techniques and material. FHH and DS analyzed the data and wrote the manuscript.

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Author notes

  1. F H Heidel and D Schlüter: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute for Medical Microbiology and Hospital Hygiene, Otto-von-Guericke University Magdeburg, Magdeburg, Germany

    G Nishanth, S Just & D Schlüter

  2. Department of Hematology and Oncology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany

    D Wolleschak, C Fahldieck, T Fischer & F Perner

  3. Division of Hematology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    A Mullally

  4. Innere Medizin II, Hämatologie und Onkologie, Universitätsklinikum Jena, Jena, Germany

    F Perner, T M Schnöder & F H Heidel

  5. Leibniz-Institute on Aging, Fritz-Lipmann-Institute, Jena, Germany

    F Perner, T M Schnöder & F H Heidel

  6. Organ-Specific Immune Regulation, Helmholtz-Center for Infection Research, Braunschweig, Germany

    D Schlüter

Authors
  1. G Nishanth
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  2. D Wolleschak
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  5. A Mullally
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  6. F Perner
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  7. T M Schnöder
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  8. S Just
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  9. F H Heidel
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  10. D Schlüter
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Corresponding authors

Correspondence to F H Heidel or D Schlüter.

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The authors declare no conflict of interest.

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Nishanth, G., Wolleschak, D., Fahldieck, C. et al. Gain of function in Jak2V617F-positive T-cells. Leukemia 31, 1000–1003 (2017). https://doi.org/10.1038/leu.2017.6

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