Increased expression of insulin-like growth factor i is associated with Ara-C resistance in leukemia Increased Expression of Insulin-Like Growth Factor I is Associated with Ara-C Resistance in Leukemia

Access this Article

Search this Article

Author(s)

    • ABE SHORI
    • Department of Rheumatology and Hematology, Tohoku University School of Medicine
    • FUNATO TADAO
    • Department of Laboratory Science, School of Health Sciences, Faculty of Medicines, Kyoto University
    • TAKAHASHI SHINICHIRO
    • Department of Infection Control and Laboratory Diagnostics, Tohoku University School of Medicine
    • YOKOYAMA HISAYUKI
    • Department of Rheumatology and Hematology, Tohoku University School of Medicine
    • YAMAMOTO JOJI
    • Department of Rheumatology and Hematology, Tohoku University School of Medicine
    • TOMIYA YASUO
    • Department of Rheumatology and Hematology, Tohoku University School of Medicine
    • ISHIZAWA KENICHI
    • Department of Rheumatology and Hematology, Tohoku University School of Medicine
    • KAMEOKA JUNICHI
    • Department of Rheumatology and Hematology, Tohoku University School of Medicine
    • KAKU MITSUO
    • Department of Infection Control and Laboratory Diagnostics, Tohoku University School of Medicine
    • HARIGAE HIDEO
    • Department of Rheumatology and Hematology, Tohoku University School of Medicine
    • SASAKI TAKESHI
    • Department of Rheumatology and Hematology, Tohoku University School of Medicine

Abstract

Resistance to cytosine arabinoside (Ara-C) is a major problem in the treatment of patients with acute myeloid leukemia (AML). In order to investigate the mechanisms involved in Ara-C resistance, the gene expression profile of Ara-C-resistant K562 human myeloid leukemia cells (K562/AC cells) was compared to that of Ara-C-sensitive K562 cells (K562 cells) by using a cDNA microarray platform. Correspondence analysis demonstrated that insulin-like growth factor I (IGF-I) gene was upregulated in K562/AC cells. The biological significance of IGF-I overexpression was further examined in vitro. When K562 cells were incubated with IGF-I ligand, they were protected from apoptosis induced by Ara-C. In contrast, a significant inhibition of growth and increase of apoptosis of K562/AC cells were induced by IGF-I receptor neutralizing antibody, or suramin, a nonspecific growth factor antagonist. Moreover, from the analysis of 27 AML patients, we have shown that IGF-I expression levels are higher in patients at refractory stage, after Ara-C combined chemotherapy, than those in patients at diagnosis. These results suggest that the inhibition of IGF-I and its downstream pathway is a valuable therapeutic approach to overcome Ara-C resistance in AML.

Journal

  • The Tohoku Journal of Experimental Medicine

    The Tohoku Journal of Experimental Medicine 209(3), 217-228, 2006-07-01

    Tohoku University Medical Press

References:  57

Codes

  • NII Article ID (NAID)
    10019253644
  • NII NACSIS-CAT ID (NCID)
    AA00863920
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00408727
  • Data Source
    CJP  IR  J-STAGE 
Page Top