{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:36:53Z","timestamp":1791113813135,"version":"4.1.0"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"46","license":[{"start":{"date-parts":[[2008,11,11]],"date-time":"2008-11-11T00:00:00Z","timestamp":1226361600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.pnas.org\/site\/misc\/userlicense.xhtml"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,11,18]]},"abstract":"<jats:p>\n                    Deregulated Myc expression drives many human cancers, including Burkitt's lymphoma and a highly aggressive subset of diffuse large cell lymphomas. Myc-driven tumors often display resistance to chemotherapeutics because of acquisition of mutations that impair the apoptosis pathway regulated by the Bcl-2 protein family. Given the need to identify new therapies for such lymphomas, we have evaluated the efficacy of ABT-737, a small molecule that mimics the action of the BH3-only proteins, natural antagonists of the prosurvival Bcl-2 proteins. ABT-737 selectively targets certain prosurvival proteins (Bcl-2, Bcl-x\n                    <jats:sub>L<\/jats:sub>\n                    , and Bcl-w) but not others (Mcl-1 and A1). We treated mice transplanted with lymphomas derived either from E\u03bc-\n                    <jats:italic>myc<\/jats:italic>\n                    transgenic mice or E\u03bc-\n                    <jats:italic>myc<\/jats:italic>\n                    mice that also expressed an E\u03bc-\n                    <jats:italic>bcl<\/jats:italic>\n                    -2 transgene. As a single agent, ABT-737 significantly prolonged the survival of mice transplanted with the\n                    <jats:italic>myc<\/jats:italic>\n                    \/\n                    <jats:italic>bcl<\/jats:italic>\n                    -2 lymphomas but was ineffective for the\n                    <jats:italic>myc<\/jats:italic>\n                    lymphomas, probably because of the relatively higher Mcl-1 levels found in the latter. Strikingly, when combined with low-dose cyclophosphamide, ABT-737 produced sustained disease-free survival of all animals transplanted with two of three\n                    <jats:italic>myc<\/jats:italic>\n                    \/\n                    <jats:italic>bcl<\/jats:italic>\n                    -2 lymphomas tested. The combination therapy was also more effective against some\n                    <jats:italic>myc<\/jats:italic>\n                    lymphomas than treatment with either agent alone. Our data suggest that antagonism of Bcl-2 with small organic compounds is an attractive approach to enhance the efficacy of conventional therapy for the treatment of Myc-driven lymphomas that over-express this prosurvival molecule.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0809957105","type":"journal-article","created":{"date-parts":[[2008,11,11]],"date-time":"2008-11-11T20:45:21Z","timestamp":1226436321000},"page":"17961-17966","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":127,"title":["In vivo efficacy of the Bcl-2 antagonist ABT-737 against aggressive Myc-driven lymphomas"],"prefix":"10.1073","volume":"105","author":[{"given":"Kylie D.","family":"Mason","sequence":"first","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia;"},{"name":"Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3010, Australia;"},{"name":"Departments of Diagnostic Hematology, Clinical Hematology, and Bone Marrow Transplantation, Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandra J.","family":"Vandenberg","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare L.","family":"Scott","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia;"},{"name":"Department of Medical Oncology, Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew H.","family":"Wei","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia;"},{"name":"Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3010, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Cory","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia;"},{"name":"Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3010, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C. S.","family":"Huang","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew W.","family":"Roberts","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia;"},{"name":"Departments of Diagnostic Hematology, Clinical Hematology, and Bone Marrow Transplantation, Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,11,18]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207261"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-230X(08)60200-6"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa055351"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa055759"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3109\/07357900009012197"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc864"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1006\/bcmd.2000.0372"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2308"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6093263"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506654102"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-06-026500"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208300"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1575"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03579"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2006.10.006"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-2203"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-03-080325"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210028"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28281"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21433"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-5836"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2004.12.030"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2006.08.027"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210166"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/318533a0"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.167.2.353"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/79542"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/348331a0"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00756.x"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-3964"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5468.1053"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00214-3"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00213-1"},{"key":"e_1_3_3_34_2","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1200\/JCO.1996.14.9.2465","article-title":"Adult Burkitt's and Burkitt-like non-Hodgkin's lymphoma\u2013outcome for patients treated with high-dose therapy and autologous stem-cell transplantation in first remission or at relapse: Results from the European Group for Blood and Marrow Transplantation","volume":"14","author":"Sweetenham JW","year":"1996","unstructured":"JW Sweetenham, et al., Adult Burkitt's and Burkitt-like non-Hodgkin's lymphoma\u2013outcome for patients treated with high-dose therapy and autologous stem-cell transplantation in first remission or at relapse: Results from the European Group for Blood and Marrow Transplantation. 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