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

Research output: Contribution to journalArticlepeer-review

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 immunemodulating antitumor agents in CLL.

Original languageEnglish
Pages (from-to)1271-1279
Number of pages9
JournalAnnals of Hematology
Volume91
Issue number8
DOIs
StatePublished - Aug 2012

Keywords

  • ATP
  • CD39
  • CLL
  • Immune modulation
  • Tcells

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