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

Hiroyuki Yamada, Kazutoshi Iijima, Osamu Tomita, Tomoko Taguchi, Masashi Miharu, Kenichiro Kobayashi, Hajime Okita, Masahiro Saito, Toshiaki Shimizu, Nobutaka Kiyokawa

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15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)73-82
Number of pages10
JournalInternational journal of hematology
Volume97
Issue number1
DOIs
Publication statusPublished - 2013 Jan 1
Externally publishedYes

Keywords

  • Apoptosis
  • B-cell precursor ALL
  • Cell growth
  • IGF-1
  • IGFBP

ASJC Scopus subject areas

  • Hematology

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    Yamada, H., Iijima, K., Tomita, O., Taguchi, T., Miharu, M., Kobayashi, K., Okita, H., Saito, M., Shimizu, T., & Kiyokawa, N. (2013). Effects of insulin-like growth factor-1 on B-cell precursor acute lymphoblastic leukemia. International journal of hematology, 97(1), 73-82. https://doi.org/10.1007/s12185-012-1234-3