{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:09:11Z","timestamp":1790885351983,"version":"4.1.0"},"reference-count":23,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2008,1,1]],"date-time":"2008-01-01T00:00:00Z","timestamp":1199145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2008,1,1]],"date-time":"2008-01-01T00:00:00Z","timestamp":1199145600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Haematol"],"published-print":{"date-parts":[[2008]]},"abstract":"<jats:p>Acute myeloid leukemia (AML) is a malignant disease characterized by abnormal proliferation of clonal precursor cells. Although different strategies have been adopted to obtain complete remission, the disease actually progresses in about 60\u201370% of patients. Bortezomib has been used in multiple myeloma and other lymphoid malignancies because of its antitumor activity. Here we examined the sensitivity of bone marrow cells from AML patients (34 patients: 25 newly diagnosed, 4 relapsed, 5 refractory) to bortezomib alone or in combination with TRAIL, a member of the TNF family that induces apoptosis in tumor cells while sparing normal cells. Bortezomib induced cell death in blasts from each patient sample. The cytotoxic effect was dose- and time-dependent (concentration from 0.001 to 10 \u00b5&lt;i&gt;M&lt;\/i&gt; for 24 and 48 h) and was associated with a downregulation of Bcl-xL and Mcl-1, an upregulation of TRAIL-R1, TRAIL-R2, p21, activation of executioner caspases and a loss of the mitochondrial membrane potential. Moreover, low doses of bortezomib primed TRAIL-resistant AML cells for enhanced TRAIL-mediated killing. These results suggest that a combination of proteasome inhibitors and TRAIL could be effective for treating AML patients, even patients who are refractory to conventional chemotherapy.<\/jats:p>","DOI":"10.1159\/000151511","type":"journal-article","created":{"date-parts":[[2008,8,22]],"date-time":"2008-08-22T13:58:05Z","timestamp":1219413485000},"page":"19-30","source":"Crossref","is-referenced-by-count":24,"title":["Antitumor Activity of Bortezomib Alone and in Combination with Trail in Human Acute Myeloid Leukemia"],"prefix":"10.1159","volume":"120","author":[{"given":"Concetta","family":"Conticello","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luana","family":"Adamo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Vicari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Giuffrida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gioacchin","family":"Iannolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Anastasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Caruso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetano","family":"Moschetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Cupri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe 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Haematologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/151511","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/151511","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T23:18:09Z","timestamp":1715987889000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/AHA\/article\/doi\/10.1159\/000151511"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008]]},"references-count":23,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2008,10,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000151511","archive":["Portico"],"relation":{},"ISSN":["0001-5792","1421-9662"],"issn-type":[{"value":"0001-5792","type":"print"},{"value":"1421-9662","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008]]}}}