CD73-generated extracellular adenosine in chronic lymphocytic leukemia creates local conditions counteracting drug-induced cell death.

Claudio Tripodo, Tiziana Vaisitti, Marta Coscia, Davide Brusa, Simon C. Robson, Sara Serra, Gianluca Gaidano, Silvia Deaglio, Giovanni D'Arena, Alberto L. Horenstein, Fabio Malavasi, Luca Laurenti, Giorgio Inghirami, Davide Rossi

Risultato della ricerca: Article

86 Citazioni (Scopus)

Abstract

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.
Lingua originaleEnglish
pagine (da-a)6141-6152
Numero di pagine11
RivistaBlood
Volume118
Stato di pubblicazionePublished - 2011

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Cell death
B-Cell Chronic Lymphocytic Leukemia
Adenosine
Cell Death
Adenosine Diphosphate
Pharmaceutical Preparations
Purinergic Receptors
Purinergic P1 Receptors
T-cells
Blood
Adenosine Triphosphate
Chemical activation
Apoptosis
Chemotaxis
Growth
Lymph Nodes
Immunohistochemistry
T-Lymphocytes
Survival

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cita questo

Tripodo, C., Vaisitti, T., Coscia, M., Brusa, D., Robson, S. C., Serra, S., ... Rossi, D. (2011). CD73-generated extracellular adenosine in chronic lymphocytic leukemia creates local conditions counteracting drug-induced cell death. Blood, 118, 6141-6152.

CD73-generated extracellular adenosine in chronic lymphocytic leukemia creates local conditions counteracting drug-induced cell death. / Tripodo, Claudio; Vaisitti, Tiziana; Coscia, Marta; Brusa, Davide; Robson, Simon C.; Serra, Sara; Gaidano, Gianluca; Deaglio, Silvia; D'Arena, Giovanni; Horenstein, Alberto L.; Malavasi, Fabio; Laurenti, Luca; Inghirami, Giorgio; Rossi, Davide.

In: Blood, Vol. 118, 2011, pag. 6141-6152.

Risultato della ricerca: Article

Tripodo, C, Vaisitti, T, Coscia, M, Brusa, D, Robson, SC, Serra, S, Gaidano, G, Deaglio, S, D'Arena, G, Horenstein, AL, Malavasi, F, Laurenti, L, Inghirami, G & Rossi, D 2011, 'CD73-generated extracellular adenosine in chronic lymphocytic leukemia creates local conditions counteracting drug-induced cell death.', Blood, vol. 118, pagg. 6141-6152.
Tripodo, Claudio ; Vaisitti, Tiziana ; Coscia, Marta ; Brusa, Davide ; Robson, Simon C. ; Serra, Sara ; Gaidano, Gianluca ; Deaglio, Silvia ; D'Arena, Giovanni ; Horenstein, Alberto L. ; Malavasi, Fabio ; Laurenti, Luca ; Inghirami, Giorgio ; Rossi, Davide. / CD73-generated extracellular adenosine in chronic lymphocytic leukemia creates local conditions counteracting drug-induced cell death. In: Blood. 2011 ; Vol. 118. pagg. 6141-6152.
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abstract = "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.",
author = "Claudio Tripodo and Tiziana Vaisitti and Marta Coscia and Davide Brusa and Robson, {Simon C.} and Sara Serra and Gianluca Gaidano and Silvia Deaglio and Giovanni D'Arena and Horenstein, {Alberto L.} and Fabio Malavasi and Luca Laurenti and Giorgio Inghirami and Davide Rossi",
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AU - Tripodo, Claudio

AU - Vaisitti, Tiziana

AU - Coscia, Marta

AU - Brusa, Davide

AU - Robson, Simon C.

AU - Serra, Sara

AU - Gaidano, Gianluca

AU - Deaglio, Silvia

AU - D'Arena, Giovanni

AU - Horenstein, Alberto L.

AU - Malavasi, Fabio

AU - Laurenti, Luca

AU - Inghirami, Giorgio

AU - Rossi, Davide

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

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