{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:11:50Z","timestamp":1791277910942,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,2,24]],"date-time":"2012-02-24T00:00:00Z","timestamp":1330041600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Imatinib (IM) is considered the gold standard for chronic myeloid leukemia (CML) treatment, although resistance is emerging as a significant problem. The proinflammatory cytokines interleukin\u20106 (IL\u20106) and interleukin\u20108 (IL\u20108) play an important role in cell proliferation, survival, and resistance to glucocorticoid\u2010mediated cell death. Several transcription factors such as NF\u2010KB and AP\u20101 are activated in response to physiopathological increases and modulation of intracellular calcium levels. Our previous study demonstrated that lymphocytes from CML patients showed dysregulated calcium homeostasis and oxidative stress. Alteration in ionized calcium concentration in the cytosol has been implicated in the initiation of secretion, contraction, and cell proliferation. In this study, we hypothesized that IL\u20106, IL\u20108, NF\u2010kB, AP\u20101, and intracellular calcium may be used as selective and prognostic factors to address the follow\u2010up in CML patients treated with imatinib. Our results demonstrated a significant down\u2010regulation in IL\u20106 and IL\u20108 release as well as NF\u2010kB and AP\u20101 activation in lymphomonocytes from Imatinib\u2010treated patients, compared to samples from untreated patients. In parallel, IM treatment, in vivo and in vitro, were able to modulate the intracellular calcium concentration of peripheral blood mononuclear cells of CML patients by acting at the level of InsP<jats:sub>3<\/jats:sub> receptor in the endoplasmic reticulum and at the level of the purinergic receptors on plasma membrane. The results of this study show that measurements of NF\u2010kB, AP\u20101, IL\u20106, IL\u20108, and intracellular calcium in CML patients treated with Imatinib may give important information to the hematologist on diagnostic criteria and are highly predictive in patients with newly diagnosed CML. J. Cell. Physiol. 227: 2798\u20132803, 2012. \u00a9 2011 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jcp.23029","type":"journal-article","created":{"date-parts":[[2011,9,21]],"date-time":"2011-09-21T17:40:22Z","timestamp":1316626822000},"page":"2798-2803","source":"Crossref","is-referenced-by-count":65,"title":["Imatinib treatment inhibit IL\u20106, IL\u20108, NF\u2010KB and AP\u20101 production and modulate intracellular calcium in CML patients"],"prefix":"10.1002","volume":"227","author":[{"given":"Roberto","family":"Ciarcia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Teresa","family":"Vitiello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Galdiero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Pacilio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Iovane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danila","family":"d'Angelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Pagnini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Caparrotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Conti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Tomei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Florio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Giordano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,2,24]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6600956"},{"key":"e_1_2_5_3_1","doi-asserted-by":"crossref","first-page":"172","DOI":"10.4049\/jimmunol.121.1.172","article-title":"Independent stimulation of motility and theoxidative metabolic burst of human polymorphonuclear leukocytes","volume":"121","author":"Bass DA","year":"1978","journal-title":"J Immunol"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI35660"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-06-2151"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401874"},{"key":"e_1_2_5_7_1","first-page":"100","article-title":"Inhibition of the Abl protein\u2010tyrosine kinase in vitro and in vivo by a 2\u2010phenylaminopyrimidine derivative","volume":"56","author":"Buchdunger E","year":"1996","journal-title":"Cancer Res"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2003.08.020"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(73)90196-2"},{"key":"e_1_2_5_10_1","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.4049\/jimmunol.157.4.1371","article-title":"Murine T lymphocytes modulate activity of an ATP\u2010activated P2Z\u2010type purinoceptor during differentiation","volume":"157","author":"Chused TM","year":"1996","journal-title":"J Immunol"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22140"},{"key":"e_1_2_5_12_1","first-page":"1683","article-title":"Linkage of proliferative and maturational abnormalities in chronic myelogenous leukemia and relevance to treatment","volume":"7","author":"Clarkson B","year":"1993","journal-title":"Leukemia"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.10.3343"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(95)80045-X"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/386855a0"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0596-561"},{"key":"e_1_2_5_17_1","first-page":"697a","article-title":"Activity of an ABL specific tyrosine kinase inhibitor in patients with bcr\u2010abl positive acute leukemias, including chronic myelogenous leukemia in blast crisis","volume":"94","author":"Druker BJ","year":"1999","journal-title":"Blood"},{"key":"e_1_2_5_18_1","first-page":"1750","article-title":"Modulation of IL\u20108, IL\u20101 beta, and G\u2010CSF secretion by all\u2010trans retinoic acid in acute promyelocytic leucemia","volume":"8","author":"Dubois C","year":"1994","journal-title":"Leukemia"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.22509"},{"key":"e_1_2_5_20_1","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1016\/S0021-9258(19)83641-4","article-title":"A new generation of Ca2+ indicators with greatly improved fuorescence properties","volume":"260","author":"Grynkiewicz G","year":"1985","journal-title":"J Biol Chem"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V84.9.3063.3063"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.20.7904"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-0322"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.20217"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402576"},{"key":"e_1_2_5_26_1","first-page":"193","article-title":"Interleukin\u20106 is the central tumor growth factor in vitro and in vivo in multiple myeloma","volume":"1","author":"Klein B","year":"1990","journal-title":"Eur Cytokine Netw"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V85.4.863.bloodjournal854863"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1006\/cimm.1995.1076"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)52451-6"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2408149"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-419X(00)00002-0"},{"key":"e_1_2_5_32_1","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1182\/blood.V90.1.279.279_279_289","article-title":"Interleukin\u20106 overcomes p21WAF1 upregulation and G1 growth arrest induced by dexamethasone and interferon\u2010\u03b3 in multiple myeloma cells","volume":"90","author":"Mitsuyoshi U","year":"1997","journal-title":"Blood"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204973200"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar565"},{"key":"e_1_2_5_35_1","doi-asserted-by":"crossref","first-page":"4211","DOI":"10.1523\/JNEUROSCI.19-11-04211.1999","article-title":"Mitogenic signaling by ATP\/P2Y purinergic receptors in astrocytes: Involvement of a calcium\u2010independent protein kinase C, extracellular signal\u2010regulated protein kinase pathway distinct from the phosphatidylinositol\u2010specific phospholipase C\/calcium pathway","volume":"19","author":"Neary JT","year":"1999","journal-title":"J Neurosci"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1994.tb05027.x"},{"key":"e_1_2_5_37_1","first-page":"33","article-title":"Medroxyprogesterone acetate increases anthracyclines uptake in chronic lymphatic leukaemia cells: Role of nitric oxide and lipid peroxidation","volume":"20","author":"Pagnini U","year":"2000","journal-title":"Anticancer Res"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199904293401706"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb0502-e131"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403241"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.23785"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2001-18868"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2004.03.010"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.23029","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.23029","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T23:20:16Z","timestamp":1696893616000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.23029"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,2,24]]},"references-count":42,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2012,6]]}},"alternative-id":["10.1002\/jcp.23029"],"URL":"https:\/\/doi.org\/10.1002\/jcp.23029","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,2,24]]}}}