{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:51:50Z","timestamp":1790740310921,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2010,3,30]],"date-time":"2010-03-30T00:00:00Z","timestamp":1269907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2010,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In older patients suffering from acute myelogenous leukemia (AML), aggressive chemotherapy is accompanied with high treatment\u2010related morbidity and mortality. Gemtuzumab ozogamicin (GO), a humanized monoclonal anti\u2010CD33 antibody, represents a well tolerated treatment option, but optimal treatment schedules are still unknown. Additionally, Suppressor of cytokine signaling 3 (<jats:italic>SOCS3<\/jats:italic>) inhibits the CD33\u2010induced block on cytokine\u2010induced proliferation. Consequently, a variable response of AML cells to anti\u2010CD33\u2010targeted therapy may be caused by modulation of <jats:italic>SOCS3<\/jats:italic> expression. Twenty\u2010four patients with refractory or relapsed CD33\u2010positive AML received GO as a single agent before or after conventional chemotherapy. The methylation status of the <jats:italic>SOCS3<\/jats:italic> CpG island was assessed by methylation\u2010specific polymerase chain reaction. Response (RR) and overall survival (OS) were significantly higher in 16 patients receiving chemotherapy before GO (RR 81%, OS 14.8 months) compared to three patients who received GO single agent therapy (RR 33%, OS 7.2 months) or 16 with GO before chemotherapy (RR 0% OS 2.2 months, <jats:italic>P<\/jats:italic> = 0.01 for RR and <jats:italic>P<\/jats:italic> &lt; 0.001 for OS). Methylation of the <jats:italic>SOCS3<\/jats:italic> CpG island was found in 8\/24 patients. There was a trend towards a higher RR and longer OS in patients with <jats:italic>SOCS3<\/jats:italic> hypermethylation (RR 86%, OS 25.1 months) compared to unmethylated <jats:italic>SOCS3<\/jats:italic> (RR 56%, OS 10.3 months, <jats:italic>P<\/jats:italic> = 0.09). Administration of GO a few days after chemotherapy seems to provide better response and survival compared to administration of GO directly before chemotherapy. The potential role of <jats:italic>SOCS3<\/jats:italic> hypermethylation as a biomarker should be further investigated in patients undergoing GO containing therapies. Am. J. Hematol., 2010. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajh.21723","type":"journal-article","created":{"date-parts":[[2010,3,30]],"date-time":"2010-03-30T16:06:52Z","timestamp":1269965212000},"page":"477-481","source":"Crossref","is-referenced-by-count":13,"title":["Sequence of administration and methylation of SOCS3 may govern response to gemtuzumab ozogamicin in combination with conventional chemotherapy in patients with refractory or relapsed acute myelogenous leukemia (AML)"],"prefix":"10.1002","volume":"85","author":[{"given":"Iris","family":"Middeldorf","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Galm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainhardt","family":"Osieka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar","family":"Jost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James 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