IGF-IR determines the fates of BCR/ABL leukemia

Jingjing Xie, Xiaoli Chen, Junke Zheng, Chunling Li, Satomi Stacy, Martin Holzenberger, Xuemei Hu, Chengcheng Zhang

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Background: The tyrosine kinase receptor insulin-like growth factor 1 receptor (IGF-IR) contributes to the initiation and progression of many types of malignancies. We previously showed that IGF-2, which binds IGF-IR, is an extrinsic factor that supports the ex vivo expansion of hematopoietic stem cells (HSCs). We also demonstrated that IGF-IR is not required for HSC activity in vivo. Methods and results: Here we investigated the role of IGF-IR in chronic myeloid leukemia (CML) using the retroviral BCR/ABL transplantation mouse model. Existing antibodies against IGF-IR are not suitable for flow cytometry; therefore, we generated a fusion of the human IgG Fc fragment with mutant IGF-2 that can bind to IGF-IR. We used this fusion protein to evaluate mouse primary hematopoietic populations. Through transplantation assays with IGF-IR+ and IGF-IR-cells, we demonstrated that IGF-IR is expressed on all mouse HSCs. The expression of IGF-IR is much higher on CML cells than on acute lymphoblastic leukemia (ALL) cells. The depletion of IGF-IR expression in BCR/ABL+ cells led to the development of ALL (mostly T cell ALL) but not CML. Lack of IGF-IR resulted in decreased self-renewal of the BCR/ABL+ CML cells in the serial replating assay. Conclusion: IGF-IR regulates the cell fate determination of BCR/ABL+ leukemia cells and supports the self-renewal of CML cells.

Original languageEnglish (US)
Article number3
JournalJournal of Hematology and Oncology
Volume8
Issue number1
DOIs
StatePublished - 2015

Keywords

  • Acute lymphoblastic leukemia
  • BCR/ABL
  • Chronic myeloid leukemia
  • Hematopoietic stem cells
  • IGF-IR
  • Leukemia
  • Tyrosine kinase receptor

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Oncology
  • Cancer Research

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  • Cite this

    Xie, J., Chen, X., Zheng, J., Li, C., Stacy, S., Holzenberger, M., Hu, X., & Zhang, C. (2015). IGF-IR determines the fates of BCR/ABL leukemia. Journal of Hematology and Oncology, 8(1), [3]. https://doi.org/10.1186/s13045-015-0106-8