Increased CD39 expression on CD4(+) T lymphocytes has clinical and prognostic significance in chronic lymphocytic leukemia

Ann Hematol. 2012 Aug;91(8):1271-9. doi: 10.1007/s00277-012-1425-2. Epub 2012 Feb 16.


Chronic lymphocytic leukemia (CLL) cells depend on their microenvironment for proliferation and survival. Ectonucleotidase CD39 has anti-inflammatory properties as it hydrolyzes proinflammatory extracellular ATP, generates anti-inflammatory adenosine, and also protects regulatory T cells from ATP-induced cell death. In this study, we investigated the clinical significance of CD39 expression on CD4(+) T cells in 62 patients with CLL as well as its compartmental regulation and explored the possible mechanisms for its induction. Compared to healthy individuals, CD4(+)CD39(+) lymphocytes were increased in the peripheral blood of patients with CLL and correlated with the advanced stage of disease. CD4(+)CD39(+) cells were also higher in patients with CLL, who needed therapeutic intervention, and in those who had unmutated immunoglobulin heavy chain variable region gene, were ZAP70(+) or had β2-microglobulin levels of >3 g/L. There were more CD4(+)CD39(+) lymphocytes in the bone marrow compartment than in the peripheral blood, and in vitro studies showed that CD39 can be induced on CD4(+) cells by exposure to ATP or indirectly, following B cell receptor engagement. This may support the notion that the leukemic cells contribute to create an immune-subversive environment, and perhaps to a poorer prognosis. CD39(+) may also serve as a future target for the development of novel therapies with immune-modulating antitumor agents in CLL.

MeSH terms

  • Aged
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Antigens, Surface / genetics
  • Antigens, Surface / metabolism
  • Apyrase / genetics
  • Apyrase / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / pathology
  • Case-Control Studies
  • Disease Progression
  • Female
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis*
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Up-Regulation / genetics


  • Antigens, CD
  • Antigens, Surface
  • Biomarkers, Tumor
  • Apyrase
  • CD39 antigen