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Immunological Consequences of JAK Inhibition: Friend or Foe?

  • Myeloproliferative Disorders (C Harrison, Section Editor)
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Abstract

Over the last decade, unparalleled advances have been made within the field of ‘Philadelphia chromosome’-negative myeloproliferative neoplasms (MPN) regarding both disease pathogenesis and therapeutic targeting. The discovery of deregulated JAK-STAT signalling in MPN led to the rapid development of JAK inhibitor agents, targeting both mutated and wild-type JAK, which have significantly altered the therapeutic paradigm for patients with MPN. Although the largest population treated with these agents incorporates those with myelofibrosis, increasing data supports potential usage in other MPNs such as essential thromocythaemia and polycythaemia vera. Many MPNs are associated with a hyperinflammatory state and deregulation of immune homeostasis. Over the last few years, research has focused on attempting to decipher the complex and context-dependent changes that contribute to this immune deregulation. Moreover, very recent studies have demonstrated significant JAK inhibitor-mediated effects within the T cell, natural killer cell and dendritic cell compartments following exposure to JAK inhibitors. In parallel, case reports of infections occurring following exposure to ruxolitinib, many of which are atypical, have focused research efforts on delineating JAK inhibitor-associated immunological consequences. Within this review article, we will describe what is currently known about MPN-associated immune deregulation and JAK inhibitor-mediated immunomodulation.

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Conflict of Interest

Donal P. McLornan reports honoraria, speaker’s fees paid and travel expenses covered from Novartis.

Alesia A. Khan declares no potential conflicts of interest.

Claire N. Harrison is a section editor for Current Hematologic Malignancy Reports.

Human and Animal Rights and Informed Consent

This article does not contain any studies with animal subjects performed by any of the authors. Where work by the authors concerning human subjects is quoted, this was with full ethical approval and informed consent

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  1. Department of Haematology, Guy’s and St. Thomas’ NHS Foundation Trust, London, SE1 7EH, UK

    Donal P. McLornan, Alesia A. Khan & Claire N. Harrison

  2. Department of Haematological Medicine, King’s College Hospital NHS Foundation Trust, London, SE5 9NU, UK

    Donal P. McLornan

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  1. Donal P. McLornan
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Correspondence to Donal P. McLornan.

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This article is part of the Topical Collection on Myeloproliferative Disorders

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McLornan, D.P., Khan, A.A. & Harrison, C.N. Immunological Consequences of JAK Inhibition: Friend or Foe?. Curr Hematol Malig Rep 10, 370–379 (2015). https://doi.org/10.1007/s11899-015-0284-z

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