Figure 3

Inhibition of IGFBP2 expression delays leukemia development in the AML1-ETO transplantation mouse AML model. (A) Expression of IGFBP2 in AML1-ETO infected BM Lin^-Kit⁺Sca-1^- cells and Lin^-Kit^-Sca-1^- cells as determined by real-time RT-PCR (n = 3). (B) Mice transplanted with AML1-ETO-infected wild-type hematopoietic progenitors had significantly reduced survival compared to that of mice transplanted with AML1-ETO-infected IGFBP2-null hematopoietic progenitors (n = 14; p < 0.005). (C) IGFBP2-null AML mice had fewer leukemic GFP⁺ cells in peripheral blood than mice transplanted with wild-type cells at 3–4 months after transplantation (n = 14; * p < 0.05). (D) Percentages of progenitors and differentiated cells in the control and IGFBP2-null leukemic GFP⁺ compartments of peripheral blood at four months after transplantation (n = 14). (E) Comparison of the sizes of spleens and livers of the mice transplanted with wild-type AML1-ETO9a cells and those transplanted with IGFBP2-null AML1-ETO9a cells at 4 month after transplantation (* p < 0.05). (F) Histological hematoxylin/eosin staining of AML infiltration in the livers and spleens and Wright-Giemsa staining of peripheral blood cells of mice transplanted with control or IGFBP2-null AML1-ETO9a cells. (G) Phosphorylation of AKT and STAT3 decreased in IGFBP2-null AML BM cells compared with the levels in control cells. (H) The IGFBP2-null AML BM cells from primary transplant mice showed significantly decreased colony forming ability (n = 3) and morphology changes relative to cells from mice transplanted with wild-type AML cells (n = 3, * p < 0.05).