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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • 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
Enheter & grupper
Externa organisationer
  • University of Helsinki
  • Uppsala University Hospital
  • Uppsala universitet, Historiska institutionen
  • 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
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Hematologi
Originalspråkengelska
Sidor (från-till)1108-1116
Antal sidor9
TidskriftLeukemia
Volym31
Utgivningsnummer5
StatusPublished - 2017 maj 1
PublikationskategoriForskning
Peer review utfördJa