title: Homoharringtonine, omacetaxine mepesuccinate, and chronic myeloid leukemia circa 2009.
abstract: Homoharringtonine (HHT) is a natural alkaloid that is obtained from various Cephalotaxus 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-alpha 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-resistant 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-resistant CML, including those who carry the tyrosine kinase inhibitor-insensitive 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-of-the-art treatment algorithms for CML.
authors.affiliation: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. aquintas@mdanderson.org
authors.forename: Alfonso
authors.initials: A
authors.lastname: Quintás-Cardama
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
mesh_terms: D000465:Algorithms; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D001549:Benzamides; D002986:Clinical Trials as Topic; D055808:Drug Discovery; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006248:Harringtonines / Q000737:chemistry / Q000627:therapeutic use*; D000077863:Homoharringtonine; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics; D010879:Piperazines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001549:Benzamides; D006248:Harringtonines; D010879:Piperazines; D011743:Pyrimidines; D000077863:Homoharringtonine; D000068877:Imatinib Mesylate