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

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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.

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Acknowledgment

This work was supported by a grant from the Eldor-Matzner award, Chief Scientist Office, Israel Ministry of Health.

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Authors and Affiliations

  1. Department of Hematology and Bone Marrow Transplantation, Tel Aviv Sourasky Medical Center, 6 Weizman Street, Tel Aviv, Israel, 64239

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

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel

    Dan Grisaru & Elizabeth Naparstek

  3. Department of Hematology, Hadassah Medical Center, The Hebrew University, Jerusalem, Israel

    Aaron Polliack

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  1. Chava Perry
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  2. Inbal Hazan-Halevy
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  3. Sigi Kay
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  4. Michal Cipok
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  5. Dan Grisaru
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  6. Varda Deutsch
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  7. Aaron Polliack
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  8. Elizabeth Naparstek
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  9. Yair Herishanu
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Corresponding author

Correspondence to Chava Perry.

Additional information

Chava Perry and Inbal Hazan-Halevy equally contributed to this work.

Electronic supplementary material

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Supplement 1

Consecutive measurements of %CD4+CD39+ lymphocytes in individual CLL patients (DOCX 26 kb)

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Perry, C., Hazan-Halevy, I., Kay, S. et al. Increased CD39 expression on CD4+ T lymphocytes has clinical and prognostic significance in chronic lymphocytic leukemia. Ann Hematol 91, 1271–1279 (2012). https://doi.org/10.1007/s00277-012-1425-2

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  • DOI: https://doi.org/10.1007/s00277-012-1425-2

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