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
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- ABE SHORI
- Department of Rheumatology and Hematology, Tohoku University School of Medicine
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- FUNATO TADAO
- Department of Laboratory Science, School of Health Sciences, Faculty of Medicines, Kyoto University
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- TAKAHASHI SHINICHIRO
- Department of Infection Control and Laboratory Diagnostics, Tohoku University School of Medicine
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- YOKOYAMA HISAYUKI
- Department of Rheumatology and Hematology, Tohoku University School of Medicine
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- YAMAMOTO JOJI
- Department of Rheumatology and Hematology, Tohoku University School of Medicine
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- TOMIYA YASUO
- Department of Rheumatology and Hematology, Tohoku University School of Medicine
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- YAMADA FUJIWARA MINAMI
- Department of Rheumatology and Hematology, Tohoku University School of Medicine
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- ISHIZAWA KENICHI
- Department of Rheumatology and Hematology, Tohoku University School of Medicine
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- KAMEOKA JUNICHI
- Department of Rheumatology and Hematology, Tohoku University School of Medicine
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- KAKU MITSUO
- Department of Infection Control and Laboratory Diagnostics, Tohoku University School of Medicine
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- HARIGAE HIDEO
- Department of Rheumatology and Hematology, Tohoku University School of Medicine
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- SASAKI TAKESHI
- Department of Rheumatology and Hematology, Tohoku University School of Medicine
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Author(s)
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- 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
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- TAKAHASHI SHINICHIRO
- Department of Infection Control and Laboratory Diagnostics, Tohoku University School of Medicine
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- YOKOYAMA HISAYUKI
- Department of Rheumatology and Hematology, Tohoku University School of Medicine
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- YAMAMOTO JOJI
- Department of Rheumatology and Hematology, Tohoku University School of Medicine
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- TOMIYA YASUO
- Department of Rheumatology and Hematology, Tohoku University School of Medicine
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- YAMADA FUJIWARA MINAMI
- Department of Rheumatology and Hematology, Tohoku University School of Medicine
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- ISHIZAWA KENICHI
- Department of Rheumatology and Hematology, Tohoku University School of Medicine
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- KAMEOKA JUNICHI
- Department of Rheumatology and Hematology, Tohoku University School of Medicine
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- KAKU MITSUO
- Department of Infection Control and Laboratory Diagnostics, Tohoku University School of Medicine
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- HARIGAE HIDEO
- Department of Rheumatology and Hematology, Tohoku University School of Medicine
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- 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
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- The Tohoku Journal of Experimental Medicine
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The Tohoku Journal of Experimental Medicine 209(3), 217-228, 2006-07-01
Tohoku University Medical Press
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