Annals of Hematology

, Volume 91, Issue 8, pp 1271–1279

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

  • Chava Perry
  • Inbal Hazan-Halevy
  • Sigi Kay
  • Michal Cipok
  • Dan Grisaru
  • Varda Deutsch
  • Aaron Polliack
  • Elizabeth Naparstek
  • Yair Herishanu
Original Article

Abstract

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.

Keywords

CLL CD39 T cells ATP Immune modulation 

Supplementary material

277_2012_1425_MOESM1_ESM.docx (27 kb)
Supplement 1Consecutive measurements of %CD4+CD39+ lymphocytes in individual CLL patients (DOCX 26 kb)

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Chava Perry
    • 1
  • Inbal Hazan-Halevy
    • 1
  • Sigi Kay
    • 1
  • Michal Cipok
    • 1
  • Dan Grisaru
    • 1
    • 2
  • Varda Deutsch
    • 1
  • Aaron Polliack
    • 1
    • 3
  • Elizabeth Naparstek
    • 1
    • 2
  • Yair Herishanu
    • 1
  1. 1.Department of Hematology and Bone Marrow TransplantationTel Aviv Sourasky Medical CenterTel AvivIsrael
  2. 2.Sackler Faculty of MedicineTel Aviv UniversityTel-AvivIsrael
  3. 3.Department of Hematology, Hadassah Medical CenterThe Hebrew UniversityJerusalemIsrael

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