Zoledronate synergises with imatinib mesylate to inhibit Ph primary leukaemic cell growth.
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.
Segawa
Hidekazu
H
Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, Japan.
Kimura
Shinya
S
Kuroda
Junya
J
Sato
Kiyoshi
K
Yokota
Asumi
A
Kawata
Eri
E
Kamitsuji
Yuri
Y
Ashihara
Eishi
E
Yuasa
Takeshi
T
Fujiyama
Yoshihide
Y
Ottmann
Oliver G
OG
Maekawa
Taira
T
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
D001549:Benzamides; D004164:Diphosphonates; D007093:Imidazoles; D010879:Piperazines; D011743:Pyrimidines; D000077211:Zoledronic Acid; D000068877:Imatinib Mesylate