title: Increased CD39 expression on CD4(+) T lymphocytes has clinical and prognostic significance in chronic lymphocytic leukemia.
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.
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Tel Aviv Sourasky Medical Center, 6 Weizman Street, Tel Aviv, Israel 64239. chavap@tasmc.health.gov.il
authors.forename: Chava
authors.initials: C
authors.lastname: Perry
authors.forename: Inbal
authors.initials: I
authors.lastname: Hazan-Halevy
authors.forename: Sigi
authors.initials: S
authors.lastname: Kay
authors.forename: Michal
authors.initials: M
authors.lastname: Cipok
authors.forename: Dan
authors.initials: D
authors.lastname: Grisaru
authors.forename: Varda
authors.initials: V
authors.lastname: Deutsch
authors.forename: Aaron
authors.initials: A
authors.lastname: Polliack
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Naparstek
authors.forename: Yair
authors.initials: Y
authors.lastname: Herishanu
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D001081:Apyrase / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015854:Up-Regulation / Q000235:genetics
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D001081:Apyrase; C067869:CD39 antigen