{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:16:09Z","timestamp":1769040969640,"version":"3.49.0"},"reference-count":77,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2009,9,8]],"date-time":"2009-09-08T00:00:00Z","timestamp":1252368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2009,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Homoharringtonine (HHT) is a natural alkaloid that is obtained from various <jats:italic>Cephalotaxus<\/jats:italic> species. The mechanism of action by which HHT exerts its antitumor activity is through inhibition of protein synthesis and promotion of apoptosis. In the 1990s, HHT proved to be significantly active as salvage therapy for patients with chronic myeloid leukemia (CML) after failure on interferon\u2012\u03b1 therapy. However, the remarkable success of imatinib mesylate in the treatment of CML relegated HHT to oblivion. The development of omacetaxine mepesuccinate, a subcutaneously bioavailable semisynthetic form of HHT, and its activity in imatinib\u2010resistant CML has established this agent for the second time as a valuable option in the management of this disease. Preliminary results appear to support the use of this agent for patients who have imatinib\u2010resistant CML, including those who carry the tyrosine kinase inhibitor\u2010insensitive mutation that exchanges the amino acids threonine and isoleucine at position 315 (the T315I mutation). In this article, the authors discuss the current data on omacetaxine and the prospects of this agent to be integrated into the state\u2010of\u2010the\u2010art treatment algorithms for CML. Cancer 2009. \u00a9 2009 American Cancer Society.<\/jats:p>","DOI":"10.1002\/cncr.24601","type":"journal-article","created":{"date-parts":[[2009,9,8]],"date-time":"2009-09-08T14:50:43Z","timestamp":1252421443000},"page":"5382-5393","source":"Crossref","is-referenced-by-count":94,"title":["Homoharringtonine, omacetaxine mepesuccinate, and chronic myeloid leukemia circa 2009"],"prefix":"10.1002","volume":"115","author":[{"given":"Alfonso","family":"Quint\u00e1s\u2010Cardama","sequence":"first","affiliation":[]},{"given":"Hagop","family":"Kantarjian","sequence":"additional","affiliation":[]},{"given":"Jorge","family":"Cortes","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2009,11,19]]},"reference":[{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20010915)92:6<1591::AID-CNCR1485>3.0.CO;2-U"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(01)97839-6"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600610812"},{"key":"e_1_2_10_5_2","first-page":"319","article-title":"Harringtonine in acute leukemias. Clinical analysis of 31 cases","volume":"3","year":"1977","journal-title":"Chin Med J (Engl)."},{"key":"e_1_2_10_6_2","first-page":"263","article-title":"Cephalotaxine esters in the treatment of acute leukemia. A preliminary clinical assessment","volume":"2","year":"1976","journal-title":"Chin Med J (Engl)."},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.9.3322.bloodjournal8693322"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.12.4149"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0596-561"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2408149"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa062867"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1062538"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1099480"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.01.007"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.293.5538.2163a"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1977.tb11256.x"},{"key":"e_1_2_10_17_2","first-page":"69","article-title":"Influence of harringtonine on human leukemia cell differentiation","volume":"37","author":"Kuliczkowski K","year":"1989","journal-title":"Arch Immunol Ther Exp (Warsz)."},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.20100"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.12.2.298"},{"key":"e_1_2_10_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2400608"},{"key":"e_1_2_10_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402775"},{"key":"e_1_2_10_22_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.7.1999"},{"key":"e_1_2_10_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.10543"},{"key":"e_1_2_10_24_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-1216"},{"key":"e_1_2_10_25_2","first-page":"156","article-title":"[A preliminary therapeutic analysis of 82 cases of chronic granulocytic leukemia treated with harringtonine]","volume":"25","author":"Zhang ZY","year":"1986","journal-title":"Zhonghua Nei Ke Za Zhi."},{"key":"e_1_2_10_26_2","first-page":"283","article-title":"Studies on the antitumor constituents of Cephalotaxus hainanesis Li","volume":"34","author":"Institute of Materia Medica, Chinese Academy of Medical Services and Chinese People's Liberation Army, 187th Hospital","year":"1976","journal-title":"Acta Chim Sinica."},{"key":"e_1_2_10_27_2","first-page":"319","article-title":"The antitumor effects and pharmacologic actions of harringtonine","volume":"3","author":"Institute of Materia Medica, Chinese Academy of Medical Sciences","year":"1977","journal-title":"Chinese Med J."},{"key":"e_1_2_10_28_2","first-page":"163","article-title":"Homoharringtonine in the treatment of leukemias: clinical analysis of 72 cases","volume":"3","author":"Chinese People's Liberation Army, 187th Hospital","year":"1978","journal-title":"Chinese Med J."},{"key":"e_1_2_10_29_2","first-page":"1085","article-title":"Phase I clinical investigation of homoharringtonine","volume":"68","author":"Legha SS","year":"1984","journal-title":"Cancer Treat Rep."},{"key":"e_1_2_10_30_2","first-page":"693","article-title":"Phase I trial of homoharringtonine administered as a 5\u2010day continuous infusion","volume":"67","author":"Coonley CJ","year":"1983","journal-title":"Cancer Treat Rep."},{"key":"e_1_2_10_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00179432"},{"key":"e_1_2_10_32_2","first-page":"801","article-title":"Phase I trial of homoharringtonine","volume":"67","author":"Neidhart JA","year":"1983","journal-title":"Cancer Treat Rep."},{"key":"e_1_2_10_33_2","first-page":"359","article-title":"Phase I study of homoharringtonine (NSC 141\u2010633)","volume":"26","author":"Whitacre MY","year":"1985","journal-title":"Proc Am Soc Clin Oncol."},{"key":"e_1_2_10_34_2","first-page":"967","article-title":"Phase I trial of homoharringtonine administered by prolonged continuous infusion","volume":"46","author":"Neidhart JA","year":"1986","journal-title":"Cancer Res."},{"key":"e_1_2_10_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02427837"},{"key":"e_1_2_10_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00180819"},{"key":"e_1_2_10_37_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1006327418043"},{"key":"e_1_2_10_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00170872"},{"key":"e_1_2_10_39_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1985.3.5.617"},{"key":"e_1_2_10_40_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000421-198812000-00006"},{"key":"e_1_2_10_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19890301)63:5<813::AID-CNCR2820630502>3.0.CO;2-V"},{"key":"e_1_2_10_42_2","first-page":"1185","article-title":"Homoharringtonine is safe and effective for patients with acute myelogenous leukemia","volume":"6","author":"Feldman E","year":"1992","journal-title":"Leukemia."},{"key":"e_1_2_10_43_2","first-page":"2990","article-title":"Phase I and clinical pharmacological study of 4\u2010demethoxydaunorubicin (idarubicin) in children with advanced cancer","volume":"47","author":"Tan CT","year":"1987","journal-title":"Cancer Res."},{"key":"e_1_2_10_44_2","first-page":"160","article-title":"Phase I\/II trial of homoharringtonine in acute leukemia","volume":"6","author":"Arlin Z","year":"1987","journal-title":"Proc Am Soc Clin Oncol."},{"key":"e_1_2_10_45_2","first-page":"1189","article-title":"Homoharringtonine in combination with cytarabine for patients with acute myelogenous leukemia","volume":"6","author":"Feldman E","year":"1992","journal-title":"Leukemia."},{"key":"e_1_2_10_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.11620"},{"key":"e_1_2_10_47_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2000.18.20.3513"},{"key":"e_1_2_10_48_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-008-0805-8"},{"key":"e_1_2_10_49_2","first-page":"571a","article-title":"Homoharringtonine and low\u2010dose ara\u2010C is a highly effective combination for the treatment of CML in chronic phase","volume":"90","author":"Ernst T","year":"1997","journal-title":"Blood (ASH Annual Meeting Abstracts)."},{"key":"e_1_2_10_50_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.10436"},{"key":"e_1_2_10_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(99)00327-5"},{"key":"e_1_2_10_52_2","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-05-0164"},{"key":"e_1_2_10_53_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.8.3516"},{"key":"e_1_2_10_54_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2007.06899.x"},{"key":"e_1_2_10_55_2","doi-asserted-by":"publisher","DOI":"10.1080\/10428190701411466"},{"key":"e_1_2_10_56_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-008-0081-8"},{"key":"e_1_2_10_57_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1745-7270.2007.00364.x"},{"key":"e_1_2_10_58_2","volume-title":"Analysis of transcription factor expression after homoharringtonine treatment","author":"Michaels S","year":"2007"},{"key":"e_1_2_10_59_2","article-title":"Inhibitory effects of homoharringtonine on leukemic stem cells and BCR\u2010ABL induced chronic myeloid leukemia and acute lymphoblastic leukemia in mice","volume":"110","author":"Chen Y","year":"2007","journal-title":"Blood (ASH Annual Meeting Abstracts)."},{"key":"e_1_2_10_60_2","first-page":"908a","article-title":"Semi\u2010synthetic homoharringtonine (Myelostat\u00ae) for chronic myeloid leukemia in accelerated phase after imatinib failure","volume":"102","author":"Burton C","year":"2003","journal-title":"Blood (ASH Annual Meeting Abstracts)."},{"key":"e_1_2_10_61_2","first-page":"909a","article-title":"Subcutaneous hemi\u2010synthetic homoharringtonine (HHT) in combination with imatinib mesylate (Gleevec) in patients (PTS) with STI\u2010resistant chronic myelogenous leukemia (CML): preliminary results of a pilot study","volume":"102","author":"Maloisel F","year":"2003","journal-title":"Blood (ASH Annual Meeting Abstracts)."},{"key":"e_1_2_10_62_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.22398"},{"key":"e_1_2_10_63_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20975"},{"key":"e_1_2_10_64_2","article-title":"A phase II study of intravenous (IV) homoharringtonine (HHT) and imatinib (IM) in patients (pts) with chronic myeloid leukemia (CML)","volume":"108","author":"Quintas\u2010Cardama A","year":"2006","journal-title":"Blood (ASH Annual Meeting Abstracts)."},{"key":"e_1_2_10_65_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5486.1938"},{"key":"e_1_2_10_66_2","first-page":"4236","article-title":"Crystal structures of the kinase domain of c\u2010Abl in complex with the small molecule inhibitors PD173955 and imatinib (STI\u2010571)","volume":"62","author":"Nagar B","year":"2002","journal-title":"Cancer Res."},{"key":"e_1_2_10_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1486"},{"key":"e_1_2_10_68_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200104053441402"},{"key":"e_1_2_10_69_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa055104"},{"key":"e_1_2_10_70_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa055229"},{"key":"e_1_2_10_71_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm049486a"},{"key":"e_1_2_10_72_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-06-094508"},{"key":"e_1_2_10_73_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404772"},{"key":"e_1_2_10_74_2","article-title":"Safety and efficacy of subcutaneous (SC) omacetaxine mepesuccinate in imatinib (IM)\u2010resistant chronic myeloid leukemia (CML) patients with the T315I mutation\u2014results of an ongoing multicenter phase 2\/3 study","volume":"112","author":"Cortes J","year":"2008","journal-title":"Blood (ASH Annual Meeting Abstracts)."},{"key":"e_1_2_10_75_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2324"},{"key":"e_1_2_10_76_2","doi-asserted-by":"publisher","DOI":"10.2174\/156802608784911635"},{"key":"e_1_2_10_77_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-0117"},{"key":"e_1_2_10_78_2","volume-title":"Design and evaluation of oral delivery dosage forms of homoharringtonine","author":"Brown D","year":"2007"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcncr.24601","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.24601","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T15:45:57Z","timestamp":1760283957000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.24601"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,11,19]]},"references-count":77,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2009,12]]}},"alternative-id":["10.1002\/cncr.24601"],"URL":"https:\/\/doi.org\/10.1002\/cncr.24601","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,11,19]]}}}