Mono/oligoclonal T and NK cells are common in chronic myeloid leukemia patients at diagnosis and expand during dasatinib therapy

Research output: Contribution to journalArticle

Abstract

In a proportion of patients with chronic myeloid leukemia (CML) being treated with dasatinib, we recently observed large granular lymphocyte (LGL) expansions carrying clonal T-cell receptor (TCR) gamma/delta gene rearrangements. To assess the prevalence and role of clonal lymphocytes in CML, we collected samples from patients (n = 34) at the time of diagnosis and during imatinib and dasatinib therapies and analyzed lymphocyte clonality with a sensitive polymerase chain reaction-based method of TCR gamma and delta genes. Surprisingly, at CML diagnosis, 15 of 18 patients (83%) had a sizeable clonal, BCR-ABL1 negative lymphocyte population, which was uncommon in healthy persons (1 of 12; 8%). The same clone persisted at low levels in most imatinib-treated patients. In contrast, in a distinct population of dasatinib-treated patients, the diagnostic phase clone markedly expanded, resulting in absolute lymphocytosis in blood. Most patients with LGL expansions (90%) had TCR delta rearrangements, which were uncommon in patients without an LGL expansion (10%). The TCR delta clones were confined to gamma delta(+) T- or natural killer-cell compartments and the TCR gamma clones to CD4(+)/CD8(+) alpha beta(+) fractions. The functional importance of clonal lymphocytes as a part of leukemia immune surveillance and the putative anergy- reversing role of dasatinib require further evaluation. (Blood. 2010; 116(5): 772- 782)

Details

Authors
  • Anna Kreutzman
  • Vesa Juvonen
  • Veli Kairisto
  • Marja Ekblom
  • Leif Stenke
  • Ruth Seggewiss
  • Kimmo Porkka
  • Satu Mustjoki
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Hematology
Original languageEnglish
Pages (from-to)772-782
JournalBlood
Volume116
Issue number5
Publication statusPublished - 2010
Publication categoryResearch
Peer-reviewedYes