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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
CD73-generated extracellular adenosine in chronic lymphocytic leukemia creates local conditions counteracting drug-induced cell death
Blood, Volume 118, No. 23, Year 2011
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Description
Extracellular adenosine (ADO), generated from ATP or ADP through the concerted action of the ectoenzymes CD39 and CD73, elicits autocrine and paracrine effects mediated by type 1 purinergic receptors. We have tested whether the expression of CD39 and CD73 by chronic lymphocytic leukemia (CLL) cells activates an adenosinergic axis affecting growth and survival. By immunohistochemistry, CD39 is widely expressed in CLL lymph nodes, whereas CD73 is restricted to proliferation centers. CD73 expression is highest on Ki-67 + CLL cells, adjacent to T lymphocytes, and is further localized to perivascular areas. CD39+/ CD73+/+ CLL cells generate ADO from ADP in a time- and concentration-dependent manner. In peripheral blood, CD73 expression occurs in 97/299 (32%) CLL patients and pairs with CD38 and ZAP-70 expression. CD73-generated extracellular ADO activates type 1 purinergic A2A receptors that are constitutively expressed by CLL cells and that are further elevated in proliferating neoplastic cells. Activation of the ADO receptors increases cytoplasmic cAMP levels, inhibiting chemotaxis and limiting spontaneous drug-induced apoptosis of CLL cells. These data are consistent with the existence of an autocrine adenosinergic loop, and support engraftment of leukemic cells in growth-favorable niches, while simultaneously protecting from the action of chemotherapeutic agents. © 2011 by The American Society of Hematology.
Authors & Co-Authors
Rossi, Davide
Italy, Vercelli
Università Degli Studi Del Piemonte Orientale Amedeo Avogadro
Laurenti, Luca
Italy, Rome
Università Cattolica Del Sacro Cuore, Campus Di Roma
Coscia, Marta A.
Italy, Turin
Azienda Sanitaria Ospedaliera Molinette San Giovanni Battista Di Torino
Tripodo, Claudio
Italy, Palermo
Università Degli Studi Di Palermo
Inghirami, Giorgio G.
Unknown Affiliation
Robson, Simon Christopher
United States, Boston
Beth Israel Deaconess Medical Center
Gaidano, Gianluca
Italy, Vercelli
Università Degli Studi Del Piemonte Orientale Amedeo Avogadro
Malavasi, Fabio
Italy, Turin
Università Degli Studi Di Torino
Statistics
Citations: 132
Authors: 8
Affiliations: 7
Identifiers
Doi:
10.1182/blood-2011-08-374728
ISSN:
00064971
Research Areas
Cancer