Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia

Research output: Contribution to journalArticle

Abstract

Recent studies suggest that a proportion of chronic myeloid leukemia (CML) patients in deep molecular remission can discontinue the tyrosine kinase inhibitor (TKI) treatment without disease relapse. In this multi-center, prospective clinical trial (EURO-SKI, NCT01596114) we analyzed the function and phenotype of T and NK cells and their relation to successful TKI cessation. Lymphocyte subclasses were measured from 100 imatinib-treated patients at baseline and 1 month after the discontinuation, and functional characterization of NK and T cells was done from 45 patients. The proportion of NK cells was associated with the molecular relapse-free survival as patients with higher than median NK-cell percentage at the time of drug discontinuation had better probability to stay in remission. Similar association was not found with T or B cells or their subsets. In non-relapsing patients the NK-cell phenotype was mature, whereas patients with more naïve CD56bright NK cells had decreased relapse-free survival. In addition, the TNF-α/IFN-γ cytokine secretion by NK cells correlated with the successful drug discontinuation. Our results highlight the role of NK cells in sustaining remission and strengthen the status of CML as an immunogenic tumor warranting novel clinical trials with immunomodulating agents.

Details

Authors
  • M. Ilander
  • U. Olsson-Strömberg
  • H. Schlums
  • J. Guilhot
  • O. Brück
  • H. Lähteenmäki
  • T. Kasanen
  • P. Koskenvesa
  • S. Söderlund
  • B. Markevärn
  • A. Själander
  • K. Lotfi
  • A. Dreimane
  • A. Lübking
  • M. Björeman
  • S. Lehmann
  • L. Stenke
  • L. Ohm
  • T. Gedde-Dahl
  • W. Majeed
  • S. Koskela
  • S. Saussele
  • F. X. Mahon
  • K. Porkka
  • H. Hjorth-Hansen
  • Y. T. Bryceson
  • S. Mustjoki
Organisations
External organisations
  • University of Helsinki
  • Uppsala University Hospital
  • Uppsala University
  • Karolinska University Hospital
  • Poitiers University Hospital
  • Norrland University Hospital
  • Umeå University
  • Linköping University Hospital
  • Skåne University Hospital
  • Örebro University Hospital
  • Norwegian Radium Hospital
  • Stavanger University Hospital
  • Finnish Red Cross Blood Transfusion Service
  • Heidelberg University
  • St. Olav’s University Hospital
  • University of Bordeaux
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Hematology
Original languageEnglish
Pages (from-to)1108-1116
Number of pages9
JournalLeukemia
Volume31
Issue number5
Publication statusPublished - 2017 May 1
Publication categoryResearch
Peer-reviewedYes