Case Report

International Journal of Hematology

, Volume 79, Issue 1, pp 37-43

Antiproliferative Efficacy of the Third-Generation Bisphosphonate, Zoledronic Acid, Combined with Other Anticancer Drugs in Leukemic Cell Lines

  • Shinya KimuraAffiliated withDepartment of Transfusion Medicine and Cell Therapy, Kyoto University Hospital Email author 
  • , Junya KurodaAffiliated withDepartment of Transfusion Medicine and Cell Therapy, Kyoto University HospitalDepartment of Internal Medicine, Kyoto Prefectural University of Medicine
  • , Hidekazu SegawaAffiliated withDepartment of Transfusion Medicine and Cell Therapy, Kyoto University HospitalDepartment of Gastroenterology and Hematology, Shiga University of Medical Science
  • , Kiyoshi SatoAffiliated withDepartment of Transfusion Medicine and Cell Therapy, Kyoto University HospitalDepartment of Thoracic Surgery, Faculty of Medicine, Kyoto University
  • , Masaki NogawaAffiliated withDepartment of Transfusion Medicine and Cell Therapy, Kyoto University Hospital
  • , Takeshi YuasaAffiliated withDepartment of Transfusion Medicine and Cell Therapy, Kyoto University Hospital
  • , Oliver G. OttmannAffiliated withDepartment of Hematology, Johann Wolfgang Goethe University
  • , Taira MaekawaAffiliated withDepartment of Transfusion Medicine and Cell Therapy, Kyoto University Hospital

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Abstract

Bisphosphonates are widely used to treat bone diseases and appear to possess antitumor activity. Moreover, we recently found that a third-generation bisphosphonate, zoledronic acid (ZOL), synergistically interacts with imatinib in vitro and in vivo to induce antileukemic activity, and others have reported that ZOL interacts synergistically with paclitaxel. Thus, the efficacy of other antileukemic agents combined with ZOL should be evaluated experimentally. In this study, we investigated the effects of concurrent and sequential combinations of ZOL with several commonly used antileukemic agents, including imatinib, on the in vitro growth of leukemia cell lines. As a complement to our previous finding that ZOL synergistically augments the effects of imatinib, we report here that ZOL acts additively when administered concurrently with hydroxyurea (HU), cytarabine (Ara-C), or daunorubicin (DNR) in some leukemic cell lines. Furthermore, one day of ZOL pretreatment augmented the sensitivity of imatinib and Ara-C. Therefore, concurrent or sequential administration of ZOL with imatinib, HU, Ara-C, or DNR may increase the efficacy of leukemia treatment.

Key words

Zoledronic acid Cytarabine Imatinib Leukemia Combination therapy