{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T10:03:49Z","timestamp":1771236229781,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,8,27]],"date-time":"2015-08-27T00:00:00Z","timestamp":1440633600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Helmholtz Alliance on Immunotherapy of Cancer"},{"name":"Deutsches Konsortium f\u00fcr Translationale Krebsforschung (DKTK)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2016,1,15]]},"abstract":"<jats:p>Over\u2010expression of Bcl\u20102, Bcl\u2010x<jats:sub>L<\/jats:sub> and Bcl\u2010w is frequently associated with cancer resistance to chemotherapy. Navitoclax (ABT\u2010263), an orally bio\u2010available small\u2010molecule mimetic of the Bcl\u20102 homology domain 3, specifically inhibits Bcl\u20102, Bcl\u2010x<jats:sub>L<\/jats:sub> and Bcl\u2010w. Despite promising results obtained from the clinical trials, the use of Navitoclax in patients is dose\u2010limited due to induction of death of platelets <jats:italic>via<\/jats:italic> inhibition of Bcl\u2010x<jats:sub>L<\/jats:sub> and subsequent thrombocytopenia. This side effect limits the use of Navitoclax in low doses and to very sensitive tumors. In this study, we show that HTLV\u20101\u2010associated adult T\u2010cell leukemia\/lymphoma (ATL) cells, which over\u2010express Bcl\u20102, Bcl\u2010xL and Bcl\u2010w, show a 10\u2010 to 20\u2010fold higher sensitivity (EC<jats:sub>50<\/jats:sub>\u2009=\u2009\u223c25\u201350 nM) to Navitoclax compared to non\u2010HTLV\u20101\u2010associated leukemic cells (EC<jats:sub>50<\/jats:sub>\u2009=\u2009\u223c1 \u03bcM). Investigation of the molecular mechanisms revealed that the HTLV\u20101 oncogenic protein Tax up\u2010regulates expression of the pro\u2010apoptotic protein Bax which enhances the therapeutic efficacy of Navitoclax. In addition, we show that agents that inhibit the transcription elongation or translation initiation such as Wogonin and Roc\u2010A can further decrease the effective dose of Navitoclax. Our study suggests that HTLV\u20101 ATL may be a good candidate disease for low dose Navitoclax therapy and probably with less risk of thrombocytopenia.<\/jats:p>","DOI":"10.1002\/ijc.29726","type":"journal-article","created":{"date-parts":[[2015,8,11]],"date-time":"2015-08-11T09:02:48Z","timestamp":1439283768000},"page":"507-514","source":"Crossref","is-referenced-by-count":13,"title":["HTLV\u20101\u2010associated adult <scp>T<\/scp> cell leukemia is highly susceptible to <scp>N<\/scp>avitoclax due to enhanced <scp>B<\/scp>ax expression"],"prefix":"10.1002","volume":"138","author":[{"given":"Mathias","family":"Witzens\u2010Harig","sequence":"first","affiliation":[{"name":"Medizinische Klinik V, Hematology, Oncology Und Rheumatology University Heidelberg Heidelberg 69120 Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Giaisi","sequence":"additional","affiliation":[{"name":"Tumorimmunology Program (D030) German Cancer Research Center (DKFZ) Heidelberg D\u201069120 Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"K\u00f6hler","sequence":"additional","affiliation":[{"name":"Tumorimmunology Program (D030) German Cancer Research Center (DKFZ) Heidelberg D\u201069120 Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter H.","family":"Krammer","sequence":"additional","affiliation":[{"name":"Tumorimmunology Program (D030) German Cancer Research Center (DKFZ) Heidelberg D\u201069120 Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Li\u2010Weber","sequence":"additional","affiliation":[{"name":"Tumorimmunology Program (D030) German Cancer Research Center (DKFZ) Heidelberg D\u201069120 Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,8,27]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2658"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-5836"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-3090"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70261-8"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.34.7898"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-03-344812"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2111"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2012.00388"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.537"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.11.9958"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.28.0669"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-10-247510"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2011.571207"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.10.6476"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.77.12.7415"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2992081"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0145-2126(95)00030-R"},{"key":"e_1_2_6_19_1","first-page":"269","article-title":"Immediate effects of reversible HTLV\u20101 tax function: T\u2010cell activation and apoptosis","volume":"10","author":"Chlichlia K","year":"1995","journal-title":"Oncogene"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29009"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1593\/neo.03388"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.11316"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2006.10.006"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-2203"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2006.08.027"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-3964"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-008-8637-6"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29013"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-7091-0748-5_1"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2010.179"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2007.02.049"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M302637200"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210492"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202608"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-230X(03)01003-0"},{"key":"e_1_2_6_36_1","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1182\/blood.V85.7.1865.bloodjournal8571865","article-title":"Human T\u2010cell leukemia virus type\u20101 (HTLV\u20101) Tax is expressed at the same level in infected cells of HTLV\u20101\u2013associated myelopathy or tropical spastic paraparesis patients as in asymptomatic carriers but at a lower level in adult T\u2010cell leukemia cells","volume":"85","author":"Furukawa Y","year":"1995","journal-title":"Blood"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2011.11.030"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.29726","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.29726","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T07:15:33Z","timestamp":1696403733000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.29726"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8,27]]},"references-count":36,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,1,15]]}},"alternative-id":["10.1002\/ijc.29726"],"URL":"https:\/\/doi.org\/10.1002\/ijc.29726","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,8,27]]}}}