title: IGF binding protein 2 is a cell-autonomous factor supporting survival and migration of acute leukemia cells.
abstract: BACKGROUND
  The role of IGF binding protein 2 (IGFBP2) in cancer development is intriguing. Previously we identified IGFBP2 as an extrinsic factor that supports the activity of hematopoietic stem cells (HSCs).
  
  
  RESULTS
  Here we investigated the role of IGFBP2 in in human leukemia cells and in the retroviral AML1-ETO9a transplantation acute myeloid leukemia (AML) mouse model.
  
  
  RESULTS
  IGFBP2 is highly expressed in certain human AML and acute lymphoblastic leukemia (ALL) cells. Inhibition of expression of endogenous IGFBP2 in human leukemia cells led to elevated apoptosis and decreased migration and, consistently, to decreased activation of AKT and other signaling molecules. We also studied the effects of IGFBP2 knockout in the retroviral AML1-ETO9a transplantation AML mouse model. The deletion of IGFBP2 in donor AML cells significantly decreased leukemia development in transplanted mice. Lack of IGFBP2 resulted in upregulation of PTEN expression and downregulation of AKT activation, in the mouse AML cells. The treatment of IGFBP2 deficient AML cells with a PTEN inhibitor restored the wild-type colony forming ability. The deletion of IGFBP2 also led to decreased AML infiltration into peripheral organs and tissues, suggesting that IGFBP2 is required for the migration of AML cells out of bone marrow.
  
  
  CONCLUSIONS
  IGFBP2 is a critical cell-autonomous factor that promotes the survival and migration of acute leukemia cells.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Chen
authors.forename: Junke
authors.initials: J
authors.lastname: Zheng
authors.forename: Yizhou
authors.initials: Y
authors.lastname: Zou
authors.forename: Chun
authors.initials: C
authors.lastname: Song
authors.forename: Xuemei
authors.initials: X
authors.lastname: Hu
authors.affiliation: Departments of Physiology and Developmental Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas 75390, TX, USA. alec.zhang@utsouthwestern.edu.
authors.forename: Cheng Cheng
authors.initials: CC
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D004195:Disease Models, Animal; D057809:HEK293 Cells; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015398:Signal Transduction
chemical_list: D018971:Insulin-Like Growth Factor Binding Protein 2