Premium
Zoledronate synergises with imatinib mesylate to inhibit Ph + primary leukaemic cell growth
Author(s) -
Segawa Hidekazu,
Kimura Shinya,
Kuroda Junya,
Sato Kiyoshi,
Yokota Asumi,
Kawata Eri,
Kamitsuji Yuri,
Ashihara Eishi,
Yuasa Takeshi,
Fujiyama Yoshihide,
Ottmann Oliver G.,
Maekawa Taira
Publication year - 2005
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2005.05648.x
Subject(s) - imatinib mesylate , imatinib , clone (java method) , cancer research , pharmacology , mesylate , chemistry , in vitro , medicine , in vivo , philadelphia chromosome , biology , biochemistry , chromosomal translocation , dna , genetics , myeloid leukemia , organic chemistry , gene
Summary 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.