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Effects of insulin-like growth factor-1 on B-cell precursor acute lymphoblastic leukemia

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Abstract

Insulin-like growth factor-1 (IGF-1) is known to be a major growth factor with effects on various cell types, including hematopoietic cells, as well as neoplasms, and is regulated by IGF-binding proteins (IGFBPs). In this study, we investigated the effects of IGF-1 on B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells. When the expression of IGF-1R in clinical samples of BCP-ALL was examined, five of thirty-two cases showed IGF-1R expression, whereas IGF-1R was expressed in most BCP-ALL cell lines. We observed that IGF-1 enhanced the proliferation of BCP-ALL cell lines that can be partially inhibited by IGFBP-1, -3, and -4, but not other IGFBPs. IGF-1 also partially inhibited dexamethasone-induced apoptosis, but not apoptosis mediated by VP-16 and irradiation. Interestingly, the proliferative effect of IGF-1 was partially blocked by inhibitors of MAPK and AKT, whereas the inhibition of dexamethasone-induced apoptosis was completely blocked by both inhibitors. Our data indicate that IGF-1 is involved in cell proliferation and apoptosis regulation in BCP-ALL cells. Since some BCP-ALL cases express IGF-1R, it appears to be a plausible target for prognostic evaluation and may represent a new therapeutic strategy.

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Acknowledgments

We thank Dr. Y. Matsuo for generous gifting of cell lines. We also thank H. Yagi for her excellent experimental assistance. This work was supported by a grant from Health and Labour Sciences Research Grants (the 3rd-term comprehensive 10-year strategy for cancer control H22-011), the Japan Health Sciences Foundation for Research on Publicly Essential Drugs and Medical Devices (KHA1002), the Grant of National Center for Child Health and Development (22A-5), Grant-in-Aid for Young Scientists (B) (23791211), and the Advanced research for medical products Mining Programme of the National Institute of Biomedical Innovation (NIBIO, 10-41, -42, -43, -44, -45).

Conflict of interest

We have no financial relationships or conflicts of interest related to this manuscript to declare.

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Authors and Affiliations

  1. Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo, 157-8535, Japan

    Hiroyuki Yamada, Kazutoshi Iijima, Osamu Tomita, Tomoko Taguchi, Masashi Miharu, Kenichiro Kobayashi, Hajime Okita & Nobutaka Kiyokawa

  2. Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan

    Hiroyuki Yamada, Osamu Tomita, Masahiro Saito & Toshiaki Shimizu

Authors
  1. Hiroyuki Yamada
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  2. Kazutoshi Iijima
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  3. Osamu Tomita
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  4. Tomoko Taguchi
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  5. Masashi Miharu
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  6. Kenichiro Kobayashi
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  7. Hajime Okita
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  8. Masahiro Saito
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  9. Toshiaki Shimizu
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  10. Nobutaka Kiyokawa
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Correspondence to Nobutaka Kiyokawa.

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Yamada, H., Iijima, K., Tomita, O. et al. Effects of insulin-like growth factor-1 on B-cell precursor acute lymphoblastic leukemia. Int J Hematol 97, 73–82 (2013). https://doi.org/10.1007/s12185-012-1234-3

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  • DOI: https://doi.org/10.1007/s12185-012-1234-3

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