title: The anti-leukemic efficacy of the third generation bisphosphonate ONO5920/YM529.
abstract: Ras proteins are frequently over-expressed in leukemia and contribute to leukemogenesis. We evaluated the anti-leukemic efficacy of a new third-generation bisphosphonate, ONO5920/YM529 (YM529). YM529 prevents the prenylation of Ras proteins and inhibited the growth of leukemic cells including a P-glycoprotein (P-gp) over-expressing cell line in a concentration- and time-dependent manner by inducing apoptosis in vitro. Moreover, YM529 synergistically augmented the anti-leukemic activities of paclitaxel and daunorubicin in vitro. Importantly, YM529 prolonged the survival of NOD/SCID mice engrafted with human primary leukemic cells. These findings indicate that the YM529 may become a novel molecular therapeutic class for treatment of leukemias.
authors.affiliation: Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, 54 Kawahara Shogoin Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Segawa
authors.forename: Shinya
authors.initials: S
authors.lastname: Kimura
authors.forename: Junya
authors.initials: J
authors.lastname: Kuroda
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Sato
authors.forename: Masaki
authors.initials: M
authors.lastname: Nogawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yuasa
authors.forename: Asumi
authors.initials: A
authors.lastname: Yokota
authors.forename: Keiko
authors.initials: K
authors.lastname: Hodohara
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Fujiyama
authors.forename: Taira
authors.initials: T
authors.lastname: Maekawa
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004164:Diphosphonates / Q000633:toxicity*; D018922:HL-60 Cells; D006801:Humans; D007093:Imidazoles / Q000633:toxicity*; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy*; D051379:Mice; D016513:Mice, SCID; D017368:Protein Prenylation / Q000187:drug effects; D014183:Transplantation, Heterologous; D018631:ras Proteins / Q000187:drug effects / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004164:Diphosphonates; D007093:Imidazoles; C087958:YM 529; D018631:ras Proteins