{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:52:30Z","timestamp":1790740350449,"version":"4.1.0"},"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2013,1,8]],"date-time":"2013-01-08T00:00:00Z","timestamp":1357603200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0053518","type":"journal-article","created":{"date-parts":[[2013,1,9]],"date-time":"2013-01-09T00:47:14Z","timestamp":1357692434000},"page":"e53518","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":51,"title":["AKT Signaling as a Novel Factor Associated with In Vitro Resistance of Human AML to Gemtuzumab Ozogamicin"],"prefix":"10.1371","volume":"8","author":[{"given":"David B.","family":"Rosen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly H.","family":"Harrington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Cordeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling Y.","family":"Leung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santosh","family":"Putta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norman","family":"Lacayo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George S.","family":"Laszlo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea J.","family":"Gudgeon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna E.","family":"Hogge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael E.","family":"Hawtin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Cesano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland B.","family":"Walter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2013,1,8]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1056\/NEJM199909303411407","article-title":"Acute myeloid leukemia","volume":"341","author":"B L\u00f6wenberg","year":"1999","journal-title":"N Engl J Med"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1182\/blood-2005-01-0178","article-title":"Drug therapy for acute myeloid leukemia","volume":"106","author":"MS Tallman","year":"2005","journal-title":"Blood"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1016\/S0140-6736(06)69780-8","article-title":"Acute myeloid leukaemia","volume":"368","author":"E Estey","year":"2006","journal-title":"Lancet"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1182\/blood-2009-07-235358","article-title":"Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet","volume":"115","author":"H D\u00f6hner","year":"2010","journal-title":"Blood"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"6198","DOI":"10.1182\/blood-2011-11-325050","article-title":"Acute myeloid leukemia stem cells and CD33-targeted immunotherapy","volume":"119","author":"RB Walter","year":"2012","journal-title":"Blood"},{"key":"ref6","first-page":"369","article-title":"Identification of patients with acute myeloblastic leukaemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial J Clin Oncol","volume":"29","author":"AK Burnett","year":"2011"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1016\/S0140-6736(12)60485-1","article-title":"Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study","volume":"379","author":"S Castaigne","year":"2012","journal-title":"Lancet"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Burnett AK, Russell NH, Hills RK, Kell J, Freeman S, et al.. (2012) Addition of Gemtuzumab Ozogamicin to Induction Chemotherapy Improves Survival in Older Patients With Acute Myeloid Leukemia. J Clin Oncol; Epub ahead of print July 30, 2012.","DOI":"10.1200\/JCO.2012.42.2964"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1182\/blood.V118.21.79.79","article-title":"Addition of gemtuzumab ozogamycin to chemotherapy improves event-free survival but not overall survival of AML patients with intermediate cytogenetics not eligible for allogeneic transplantation. Results of the GOELAMS AML 2006 IR study [abstract]","volume":"118","author":"J Delaunay","year":"2011","journal-title":"Blood"},{"key":"ref10","unstructured":"Pfizer Website. Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/media.pfizer.com\/files\/products\/mylotarg_hcp_letter.pdf\" xlink:type=\"simple\">http:\/\/media.pfizer.com\/files\/products\/mylotarg_hcp_letter.pdf<\/ext-link>. Accessed on: November 6, 2012."},{"key":"ref11","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/sj.leu.2403598","article-title":"CD33-directed therapy with gemtuzumab ozogamicin in acute myeloid leukemia: progress in understanding cytotoxicity and potential mechanisms of drug resistance","volume":"19","author":"ML Linenberger","year":"2005","journal-title":"Leukemia"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1182\/blood-2004-07-2784","article-title":"Influence of CD33 expression levels and ITIM-dependent internalization on gemtuzumab ozogamicin-induced cytotoxicity","volume":"105","author":"RB Walter","year":"2005","journal-title":"Blood"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"e24265","DOI":"10.1371\/journal.pone.0024265","article-title":"Targeted drug delivery by gemtuzumab ozogamicin: mechanism-based mathematical model for treatment strategy improvement and therapy individualization","volume":"6","author":"E Jager","year":"2011","journal-title":"PLoS One"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.cell.2004.06.028","article-title":"Single cell profiling of potentiated phospho-protein networks in cancer cells","volume":"118","author":"JM Irish","year":"2004","journal-title":"Cell"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1126\/science.1105809","article-title":"Causal protein-signaling networks derived from multiparameter single-cell data","volume":"308","author":"K Sachs","year":"2005","journal-title":"Science"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"3721","DOI":"10.1158\/1078-0432.CCR-10-0093","article-title":"Dynamic single-cell network profiles in acute myelogenous leukemia are associated with patient response to standard induction therapy","volume":"16","author":"SM Kornblau","year":"2010","journal-title":"Clin Cancer Res"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1002\/ijc.2910170504","article-title":"Establishment and characterization of a human histiocytic lymphoma cell line (U-937)","volume":"17","author":"C Sundstr\u00f6m","year":"1976","journal-title":"Int J Cancer"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1126\/science.306682","article-title":"Acute myelogenous leukemia: a human cell line responsive to colony-stimulating activity","volume":"200","author":"HP Koeffler","year":"1978","journal-title":"Science"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/0145-2126(82)90055-8","article-title":"Establishment and characterization of a new permanent cell line (GDM-1) from a patient with myelomonoblastic leukemia","volume":"6","author":"H Ben-Bassat","year":"1982","journal-title":"Leuk Res"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/270347a0","article-title":"Continuous growth and differentiation of human myeloid leukaemic cells in suspension culture","volume":"270","author":"SJ Collins","year":"1977","journal-title":"Nature"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1182\/blood.V77.5.1080.1080","article-title":"NB4, a maturation inducible cell line with t(15;17) marker isolated from a human acute promyelocytic leukemia (M3)","volume":"77","author":"M Lanotte","year":"1991","journal-title":"Blood"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/jcp.1041400219","article-title":"Establishment and characterization of a unique human cell line that proliferates dependently on GM-CSF, IL-3, or erythropoietin","volume":"140","author":"T Kitamura","year":"1989","journal-title":"J Cell Physiol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1182\/blood-2003-02-0396","article-title":"Multidrug resistance protein attenuates gemtuzumab ozogamicin-induced cytotoxicity in acute myeloid leukemia cells","volume":"102","author":"RB Walter","year":"2003","journal-title":"Blood"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"e12405","DOI":"10.1371\/journal.pone.0012405","article-title":"Distinct patterns of DNA damage response and apoptosis correlate with Jak\/Stat and PI3kinase response profiles in human acute myelogenous leukemia","volume":"5","author":"DB Rosen","year":"2010","journal-title":"PLoS One"},{"key":"ref25","unstructured":"Stelzer GT, Goodpasture L (2000) Use of multiparameter flow cytometry and immunophenotyping for the diagnosis and classification of acute myeloid leukemia. In: Stewart CC, Nicholson JKA, editors. Immunophenotyping. New York, NY: Wiley-Liss. 215\u2013238."},{"key":"ref26","doi-asserted-by":"crossref","first-page":"4532","DOI":"10.1158\/1078-0432.CCR-10-0523","article-title":"Histone gammaH2AX and poly(ADP-ribose) as clinical pharmacodynamic biomarkers","volume":"16","author":"CE Redon","year":"2010","journal-title":"Clin Cancer Res"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/leu.2010.6","article-title":"gammaH2AX: a sensitive molecular marker of DNA damage and repair","volume":"24","author":"LJ Mah","year":"2010","journal-title":"Leukemia"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"4276","DOI":"10.1182\/blood-2003-11-3825","article-title":"The peripheral benzodiazepine receptor ligand PK11195 overcomes different resistance mechanisms to sensitize AML cells to gemtuzumab ozogamicin","volume":"103","author":"RB Walter","year":"2004","journal-title":"Blood"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"3584","DOI":"10.1182\/blood-2005-02-0711","article-title":"PK11195, a peripheral benzodiazepine receptor (pBR) ligand, broadly blocks drug efflux to chemosensitize leukemia and myeloma cells by a pBR-independent, direct transporter-modulating mechanism","volume":"106","author":"RB Walter","year":"2005","journal-title":"Blood"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1177\/00912700122012751","article-title":"Pharmacokinetics of gemtuzumab ozogamicin, an antibody-targeted chemotherapy agent for the treatment of patients with acute myeloid leukemia in first relapse","volume":"41","author":"JA Dowell","year":"2001","journal-title":"J Clin Pharmacol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0092-8674(00)80085-9","article-title":"Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c","volume":"86","author":"X Liu","year":"1996","journal-title":"Cell"},{"key":"ref32","first-page":"459","article-title":"Technology evaluation: Valspodar, Novartis AG","volume":"2","author":"HL Tai","year":"2000","journal-title":"Curr Opin Mol Ther"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"e13543","DOI":"10.1371\/journal.pone.0013543","article-title":"Functional characterization of FLT3 receptor signaling deregulation in acute myeloid leukemia by single cell network profiling (SCNP)","volume":"5","author":"DB Rosen","year":"2010","journal-title":"PLoS One"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1002\/cyto.b.21007","article-title":"Functional pathway analysis in acute myeloid leukemia using single cell network profiling assay: Effect of specimen source (bone marrow or peripheral blood) on assay readouts","volume":"82","author":"A Cesano","year":"2012","journal-title":"Cytometry B Clin Cytom"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"e14124","DOI":"10.1371\/journal.pone.0014124","article-title":"Combination treatment with MEK and AKT inhibitors is more effective than each drug alone in human non-small cell lung cancer in vitro and in vivo","volume":"5","author":"J Meng","year":"2010","journal-title":"PLoS One"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"E577","DOI":"10.1210\/jc.2010-2644","article-title":"The Akt-specific inhibitor MK2206 selectively inhibits thyroid cancer cells harboring mutations that can activate the PI3K\/Akt pathway","volume":"96","author":"R Liu","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1158\/1535-7163.MCT-11-0606","article-title":"MK-2206, a novel allosteric inhibitor of Akt, synergizes with gefitinib against malignant glioma via modulating both autophagy and apoptosis","volume":"11","author":"Y Cheng","year":"2012","journal-title":"Mol Cancer Ther"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"811","DOI":"10.18632\/oncotarget.579","article-title":"Harnessing the PI3K\/Akt\/mTOR pathway in T-cell acute lymphoblastic leukemia: Eliminating activity by targeting at different levels","volume":"3","author":"D Bressanin","year":"2012","journal-title":"Oncotarget"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1186\/1471-2407-12-463","article-title":"Activation of AKT by hypoxia: a potential target for hypoxic tumors of the head and neck","volume":"12","author":"H Stegeman","year":"2012","journal-title":"BMC Cancer"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/j.leukres.2012.02.022","article-title":"Assessing signaling pathways associated with in vitro resistance to cytotoxic agents in AML","volume":"36","author":"DB Rosen","year":"2012","journal-title":"Leuk Res"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1038\/leu.2008.147","article-title":"Large interindividual differences in cellular sensitivity to calicheamicin may influence gemtuzumab ozogamicin response in acute myeloid leukemia","volume":"22","author":"BF Goemans","year":"2008","journal-title":"Leukemia"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1038\/sj.leu.2404245","article-title":"Phosphoinositide 3-kinase\/Akt signaling pathway and its therapeutical implications for human acute myeloid leukemia","volume":"20","author":"AM Martelli","year":"2006","journal-title":"Leukemia"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"89","DOI":"10.18632\/oncotarget.114","article-title":"The phosphatidylinositol 3-kinase\/Akt\/mTOR signaling network as a therapeutic target in acute myelogenous leukemia patients","volume":"1","author":"AM Martelli","year":"2010","journal-title":"Oncotarget"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1038\/leu.2008.395","article-title":"The level of AKT phosphorylation on threonine 308 but not on serine 473 is associated with high-risk cytogenetics and predicts poor overall survival in acute myeloid leukaemia","volume":"23","author":"N Gallay","year":"2009","journal-title":"Leukemia"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0053518","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,19]],"date-time":"2020-07-19T22:32:36Z","timestamp":1595197956000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0053518"}},"subtitle":[],"editor":[{"given":"Kristy L.","family":"Richards","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2013,1,8]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2013,1,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0053518","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,1,8]]}}}