Dissecting the Role of IGFBP-2 in Development of Acute Myeloid Leukemia
Annual rept. 1 Jun 2010-31 May 2011
TEXAS UNIV AT DALLAS SOUTHWESTERN MEDICAL CENTER
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We found that IGFBP2 supports the activity of AML stem cells and AML development. Using the retroviral MLL-AF9-IRES-YFP transplantation AML mouse model, we showed that IGFBP2 was expressed in normal hematopoietic cells, leukemia cells, and bone marrow stroma. The IGFBP2-null mice have decreased ability to develop AML in our AML mouse model, suggesting that the environmental IGFBP2 positively supports AML development. Consistently, IGFBP2 upregulated the expression of a number of oncogenes, and decreased the expression of certain tumor suppressor genes in AML stem cells. IGFBP2 is expressed by a variety of mouse bone marrow stromal cells, enriched in CD29 CD44 SSEA4 Sca-1 cells these IGFBP2- producing cells are adjacent to endothelial cells in mouse BM. The environmental effect of IGFBP2 on AML stem cells is not dependent on IGF signaling. These results, together with our flow cytometry analysis of the phenotypic AML stem cells, concluded that IGFBP2, as an environmental factor, supports the activity of AML stem cells.
- Anatomy and Physiology
- Medicine and Medical Research