Expansion of circulating CD56bright natural killer cells in patients with JAK2-positive chronic myeloproliferative neoplasms during treatment with interferon-α

Eur J Haematol. 2015 Mar;94(3):227-34. doi: 10.1111/ejh.12420. Epub 2014 Sep 24.


In recent years, major molecular remissions have been observed in patients with JAK2-positive chronic myeloproliferative neoplasms (MPNs) after therapy with IFN-α. IFN-α is known to have altering effects on immune cells involved in immune surveillance and might consequently enhance anti-tumor immune response against the JAK2-mutated clone. The objective of this study was to investigate circulating levels and phenotype of natural killer cells in 29 JAK2-positive MPN patients during IFN-α treatment. Furthermore, functional studies of NK cells upon target-cell recognition and cytokine stimulation were performed. The CD56(bright) and CD56(dim) NK cell subtypes display different properties in terms of cytokine production and cytotoxicity, respectively. Our results show a significant increase in the proportion of CD56(bright) NK cells and a decreasing CD56(dim) population during treatment with IFN-α compared to patients that are untreated, treated with hydroxyurea and healthy controls, P < 0.0001. Furthermore, an overall increase in cytokine-dependent (IL-12 and IL-15) IFN-γ expression by CD56(dim) NK cells during IFN-α treatment was observed. In contrast, our data indicate a compromised NK cell response to target-cell recognition during treatment with IFN-α in four patients. We also report low levels of circulating NK cells in untreated patients compared to healthy donors, patients treated with hydroxyurea and IFN-α, P = 0.02. Based on our findings, one might speculate whether treatment with IFN-α skews the human NK population toward a helper type that may assist in CD8(+) T cell priming in lymphoid tissues at the expense of their immediate cytotoxic functions in peripheral blood and tissues.

Keywords: IFN-α treatment; JAK2-positive MPNs; NK cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • CD56 Antigen / genetics
  • CD56 Antigen / immunology
  • Case-Control Studies
  • Female
  • Gene Expression
  • Humans
  • Hydroxyurea / therapeutic use
  • Immunologic Factors / therapeutic use*
  • Immunophenotyping
  • Interferon-alpha / therapeutic use*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interleukin-12 / biosynthesis
  • Interleukin-12 / immunology
  • Interleukin-15 / biosynthesis
  • Interleukin-15 / immunology
  • Janus Kinase 2 / genetics
  • Janus Kinase 2 / immunology
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / pathology
  • Lymphocyte Subsets / drug effects*
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / pathology
  • Male
  • Middle Aged
  • Polycythemia Vera / drug therapy*
  • Polycythemia Vera / immunology
  • Polycythemia Vera / pathology
  • Primary Myelofibrosis / drug therapy*
  • Primary Myelofibrosis / immunology
  • Primary Myelofibrosis / pathology
  • Thrombocythemia, Essential / drug therapy*
  • Thrombocythemia, Essential / immunology
  • Thrombocythemia, Essential / pathology


  • Antineoplastic Agents
  • CD56 Antigen
  • IL15 protein, human
  • Immunologic Factors
  • Interferon-alpha
  • Interleukin-15
  • NCAM1 protein, human
  • Interleukin-12
  • Interferon-gamma
  • JAK2 protein, human
  • Janus Kinase 2
  • Hydroxyurea