{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T09:16:41Z","timestamp":1791019001962,"version":"4.1.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2005,7,1]],"date-time":"2005-07-01T00:00:00Z","timestamp":1120176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The P2X7R is an ATP-gated cation channel expressed in hemopoietic cells that participates in both cell proliferation and apoptosis. Expression and function of the P2X7R have been associated with the clinical course of patients affected by chronic lymphocytic leukemia (CLL). Functional variants causing loss-of-function of the P2X7R have been identified, namely, polymorphisms 1513A&amp;gt;C (E496A), 1729T&amp;gt;A (I568N), and 946G&amp;gt;A (R307Q). Here we investigated other nonsynonymous polymorphisms located either in the extracellular portion of the receptor, such as the 489C&amp;gt;T (H155Y) variant, or in the long cytoplasmic tail of the receptor, such as the 1068G&amp;gt;A (A348T), 1096C&amp;gt;G (T357S), and 1405A&amp;gt;G (Q460R) variants. P2X7R function was monitored by measuring ATP-induced Ca2+ influx in PBL of patients affected by CLL and in recombinant human embryonic kidney (HEK) 293 cells stably transfected with each single P2X7 allelic variant. Ca2+ influx was markedly reduced in association with the 1513C allele, whereas variants located in the same intracellular domain, such as the 1068A, 1096G, or 1405G variants, were associated with a minor functional decrease. Significant Ca2+ flux increase was observed in lymphocytes from CLL patients bearing the 489C\/T and 489T\/T genotypes in association with the 1513A\/A genotype. Functional analysis in recombinant HEK293 cells expressing P2X7R confirmed an increased ATP-dependent activation of the P2X7 \u00a0489T mutant with respect to the wild type receptor, as assessed by both by [Ca2+]i influx and ethidium uptake experiments. These data identify the 489C&amp;gt;T as a gain-of-function polymorphism of the P2X7R.<\/jats:p>","DOI":"10.4049\/jimmunol.175.1.82","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T21:08:21Z","timestamp":1398028101000},"page":"82-89","source":"Crossref","is-referenced-by-count":144,"title":["A His-155 to Tyr Polymorphism Confers Gain-of-Function to the Human P2X7 Receptor of Human Leukemic Lymphocytes"],"prefix":"10.1093","volume":"175","author":[{"given":"Giulio","family":"Cabrini","sequence":"first","affiliation":[{"name":"Section of General Pathology, Department of Experimental and Diagnostic Medicine, University of Ferrara , Ferrara ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simonetta","family":"Falzoni","sequence":"additional","affiliation":[{"name":"Section of General Pathology, Department of Experimental and Diagnostic Medicine, University of Ferrara , Ferrara ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia L","family":"Forchap","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, and the Interdisciplinary Center for the Study of Inflammation, University of Ferrara , Ferrara ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Pellegatti","sequence":"additional","affiliation":[{"name":"Section of General Pathology, Department of Experimental and Diagnostic Medicine, University of Ferrara , Ferrara ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Balboni","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, and the Interdisciplinary Center for the Study of Inflammation, University of Ferrara , Ferrara ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Agostini","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Advanced Therapy, Section of Hematology, University of Ferrara , Ferrara ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Cuneo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Advanced Therapy, Section of Hematology, University of Ferrara , Ferrara ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluigi","family":"Castoldi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Advanced Therapy, Section of Hematology, University of Ferrara , Ferrara ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O Roberto","family":"Baricordi","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, and the Interdisciplinary Center for the Study of Inflammation, University of Ferrara , Ferrara ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Di Virgilio","sequence":"additional","affiliation":[{"name":"Section of General Pathology, Department of Experimental and Diagnostic Medicine, University of Ferrara , Ferrara ,","place":["Italy"]},{"name":"Interdisciplinary Center for the Study of Inflammation, University of Ferrara , Ferrara ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2005,7,1]]},"reference":[{"key":"2026020212150634400_R1","first-page":"735","volume-title":"Science","year":"1996"},{"key":"2026020212150634400_R2","first-page":"1013","volume-title":"Physiol. Rev.","year":"2002"},{"key":"2026020212150634400_R3","first-page":"5482","volume-title":"J. Biol. Chem.","year":"1997"},{"key":"2026020212150634400_R4","first-page":"347","volume-title":"Receptor Channel","year":"1998"},{"key":"2026020212150634400_R5","first-page":"3016","volume-title":"EMBO J.","year":"1998"},{"key":"2026020212150634400_R6","first-page":"335","volume-title":"J. Physiol.","year":"1999"},{"key":"2026020212150634400_R7","first-page":"33206","volume-title":"J. Biol. Chem.","year":"1999"},{"key":"2026020212150634400_R8","first-page":"13988","volume-title":"J. Biol. Chem.","year":"1994"},{"key":"2026020212150634400_R9","first-page":"8853","volume-title":"J. Biol. Chem.","year":"2003"},{"key":"2026020212150634400_R10","first-page":"11135","volume-title":"J. Biol. Chem.","year":"2001"},{"key":"2026020212150634400_R11","first-page":"5442","volume-title":"J. Immunol.","year":"2003"},{"key":"2026020212150634400_R12","first-page":"588","volume-title":"Genes Immun.","year":"2004"},{"key":"2026020212150634400_R13","first-page":"3399","volume-title":"J. Immunol.","year":"2004"},{"key":"2026020212150634400_R14","first-page":"17108","volume-title":"J. Biol. Chem.","year":"2003"},{"key":"2026020212150634400_R15","first-page":"16918","volume-title":"J. Biol. Chem.","year":"2004"},{"key":"2026020212150634400_R16","first-page":"127","volume-title":"FEBS Lett.","year":"2002"},{"key":"2026020212150634400_R17","first-page":"1458","volume-title":"J. Infect. Dis.","year":"2002"},{"key":"2026020212150634400_R18","first-page":"587","volume-title":"Blood","year":"2001"},{"key":"2026020212150634400_R19","first-page":"706","volume-title":"Blood","year":"2002"},{"key":"2026020212150634400_R20","first-page":"1114","volume-title":"Lancet","year":"2002"},{"key":"2026020212150634400_R21","first-page":"2097","volume-title":"Leukemia","year":"2003"},{"key":"2026020212150634400_R22","first-page":"1065","volume-title":"Cancer Epidemiol. Biomarkers Prev.","year":"2004"},{"key":"2026020212150634400_R23","first-page":"815","volume-title":"Br. J. Haematol.","year":"2004"},{"key":"2026020212150634400_R24","first-page":"1898","volume-title":"Lancet","year":"2002"},{"key":"2026020212150634400_R25","first-page":"1207","volume-title":"J. Clin. Invest.","year":"1995"},{"key":"2026020212150634400_R26","first-page":"959","volume-title":"Biochem. J.","year":"1988"},{"key":"2026020212150634400_R27","first-page":"2655","volume-title":"Mol. Biol. Cell.","year":"2003"},{"key":"2026020212150634400_R28","first-page":"1935","volume-title":"Lancet","year":"2002"},{"key":"2026020212150634400_R29","first-page":"66","volume-title":"Brit. J. Pharmacol.","year":"2003"},{"key":"2026020212150634400_R30","first-page":"259","volume-title":"Eur. J. Haematol.","year":"2004"},{"key":"2026020212150634400_R31","first-page":"43","volume-title":"FEBS Lett.","year":"2002"},{"key":"2026020212150634400_R32","first-page":"31287","volume-title":"J. Biol. Chem.","year":"2004"},{"key":"2026020212150634400_R33","first-page":"6347","volume-title":"EMBO J.","year":"2001"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/175\/1\/82\/62621885\/82.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/175\/1\/82\/62621885\/82.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T17:18:33Z","timestamp":1770052713000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/175\/1\/82\/8035959"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,7,1]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2005,7,1]]},"published-print":{"date-parts":[[2005,7,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.175.1.82","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2005,7]]},"published":{"date-parts":[[2005,7,1]]}}}