Phenotypic and functional deficiencies of leukaemic dendritic cells from patients with chronic myeloid leukaemia

Br J Haematol. 2003 Jan;120(1):63-73. doi: 10.1046/j.1365-2141.2003.03979.x.


Chronic myeloid leukaemia (CML) dendritic cells (DC) are possible candidates for inducing antileukaemic immunity. This study aimed to investigate the frequency, phenotype and function of blood-derived leukaemic DC in comparison with DC from healthy donors using flow cytometric assays and mixed leucocyte reaction (MLR). Immature leukaemic DC displayed a reduced endocytotic capacity as compared with healthy controls. Moreover, in vitro maturation of leukaemic DC was found to be deficient. Expression of CD80, CD83, CD86, and major histocompatibility complex class I and class II antigens were reduced on lipopolysaccharide (LPS)-matured leukaemic DC but were enhanced by a mixture of interleukin 1beta (IL-1beta), IL-6, tumour necrosis factor-alpha (TNF-alpha) and prostaglandin E2 (PGE2). Upon stimulation with bacterial LPS, intracellular TNF-alpha and IL-8 production was diminished in maturing DC from CML patients. This distinct cytokine deficiency was overcome when leukaemic DC were stimulated with cytokines/PGE2. MLR showed fully functional leukaemic DC after TNF-alpha-induced maturation, but a reduced proliferative alloresponse of leukaemic peripheral blood mononuclear cells. Further, intracellular production of cytokines in CML-derived T cells was markedly reduced. These data indicated that, in CML, the maturation response of leukaemic monocyte-derived DC to a natural stimulus like LPS is abnormal and may be caused by an aberrant TNF-alpha response in these cells. Thus, TNF-alpha alone or in combination with pro-inflammatory and T-cell stimulatory cytokines should be considered as an adjuvant for DC-based immunotherapy in CML.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Endocytosis
  • Female
  • Flow Cytometry
  • Humans
  • Immunophenotyping
  • Interleukin-2 / metabolism
  • Interleukin-4 / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology*
  • Leukocyte Count
  • Lipopolysaccharides / pharmacology
  • Lymphocyte Culture Test, Mixed
  • Male
  • Middle Aged
  • Statistics, Nonparametric
  • T-Lymphocytes / immunology
  • Tumor Necrosis Factor-alpha / metabolism


  • Interleukin-2
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Interleukin-4