Epstein-Barr virus-negative aggressive natural killer-cell leukaemia with high P-glycoprotein activity and phosphorylated extracellular signal-regulated protein kinases 1 and 2

  • Sanja Perkovic | sanja.perkovic@gmail.com Department of Laboratory Diagnostics, Division of Immunology and Department of Internal Medicine, University Hospital Centre Zagreb and School of Medicine, University of Zagreb, Croatia.
  • Sandra Basic-Kinda Division of Haematology, University Hospital Centre Zagreb and School of Medicine, University of Zagreb, Croatia.
  • Vladimir Gasparovic Division of Intensive Care Medicine, University Hospital Centre Zagreb and School of Medicine, University of Zagreb, Croatia.
  • Zeljko Krznaric Division of Gastroenterology, University Hospital Centre Zagreb and School of Medicine, University of Zagreb, Croatia.
  • Jaksa Babel Division of Intensive Care Medicine, University Hospital Centre Zagreb and School of Medicine, University of Zagreb, Croatia.
  • Ivana Ilic Department of Pathology and Cytology, Division of Gastroenterology, University Hospital Centre Zagreb and School of Medicine, University of Zagreb, Croatia.
  • Igor Aurer Division of Haematology, University Hospital Centre Zagreb and School of Medicine, University of Zagreb, Croatia.
  • Drago Batinic Department of Laboratory Diagnostics, Division of Immunology and Department of Internal Medicine, University Hospital Centre Zagreb and School of Medicine, University of Zagreb, Croatia.

Abstract

Aggressive natural killer-cell leukaemia (ANKL) is a rare type of disease with fulminant course and poor outcome. The disease is more prevalent among Asians than in other ethnic groups and shows strong association with Epstein-Barr virus (EBV) and P-glycoprotein (P-gp) expression associated with multidrug resistance. Here we present a case of a 47 year old Caucasian female with a prior medical history of azathioprine treated ulcerative colitis who developed EBV-negative form of ANKL. The patient presented with hepatosplenomegaly, fever and nausea with peripheral blood and bone marrow infiltration with up to 70% of atypical lymphoid cells positive for cCD3, CD2, CD7, CD56, CD38, CD45, TIA1 and granzyme B, and negative for sCD3, CD4, CD5, CD8, CD34 and CD123 indicative of ANKL. Neoplastic CD56+ NK-cells showed high level of P-glycoprotein expression and activity, but also strong expression of phosphorylated extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) MAP kinase. The patient was treated with an intensive polychemotherapy regimen designed for treatment of acute lymphoblastic leukaemia, but one month after admission developed sepsis, coma and died of cardiorespiratory arrest. We present additional evidence that, except for the immunophenotype, leukaemic NK-cells resemble normal NK-cells in terms of P-gp functional capacity and expression of phosphorylated ERK1/2 signalling molecule. In that sense drugs that block P-glycoprotein activity and activated signalling pathways might represent new means for targeted therapy.

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Published
2012-09-04
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Section
Case Reports
Keywords:
NK-cell leukaemia, P-glycoprotein, ERK MAP kinase, ulcerative colitis
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How to Cite
Perkovic, S., Basic-Kinda, S., Gasparovic, V., Krznaric, Z., Babel, J., Ilic, I., Aurer, I., & Batinic, D. (2012). Epstein-Barr virus-negative aggressive natural killer-cell leukaemia with high P-glycoprotein activity and phosphorylated extracellular signal-regulated protein kinases 1 and 2. Hematology Reports, 4(3), e16. https://doi.org/10.4081/hr.2012.e16