title: Zoledronate synergises with imatinib mesylate to inhibit Ph primary leukaemic cell growth.
abstract: We examined the in vivo effects and safety of the third generation bisphosphonate, zoledronate (ZOL) alone and combined with imatinib mesylate against primary Philadelphia chromosome positive (Ph+) leukaemic cells. ZOL inhibited the prenylation of Rap1A in leukaemic cells in vitro and synergised with imatinib to enhance the survival of mice engrafted with cells from imatinib-responders, but not from non-responders because of mutated BCR-ABL. These findings suggest that the combination of ZOL and imatinib accelerate the eradication of Ph+ clone, resulting in better prognosis of Ph+ leukaemia patients who have not yet acquired mutations.
authors.affiliation: Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, 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: Asumi
authors.initials: A
authors.lastname: Yokota
authors.forename: Eri
authors.initials: E
authors.lastname: Kawata
authors.forename: Yuri
authors.initials: Y
authors.lastname: Kamitsuji
authors.forename: Eishi
authors.initials: E
authors.lastname: Ashihara
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yuasa
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Fujiyama
authors.forename: Oliver G
authors.initials: OG
authors.lastname: Ottmann
authors.forename: Taira
authors.initials: T
authors.lastname: Maekawa
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols; D001549:Benzamides; D004164:Diphosphonates; D004357:Drug Synergism; D006801:Humans; D000068877:Imatinib Mesylate; D007093:Imidazoles; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D051379:Mice; D016513:Mice, SCID; D023421:Models, Animal; D009368:Neoplasm Transplantation; D010879:Piperazines; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011743:Pyrimidines; D014407:Tumor Cells, Cultured; D000077211:Zoledronic Acid
chemical_list: D001549:Benzamides; D004164:Diphosphonates; D007093:Imidazoles; D010879:Piperazines; D011743:Pyrimidines; D000077211:Zoledronic Acid; D000068877:Imatinib Mesylate