The Potential Role of Galectin-1 in Hypoxia Induced AML Cell Differentiation through C/EBPαa Transcription Regulation.

Abstract 3120

Poster Board III-57

Recently we reported that cobalt chloride-simulated hypoxia and mild hypoxia could induce the differentiation of human acute myeloid leukemic (AML) cells probably through hypoxia inducible factor-1 alpha (HIF-1αa) independent of its transcription activity. In this study, we used differential gel electrophoresis to compare the HIF-1αa regulated proteins between conditional induction and absence of HIF-1αa protein in U937T cells. Among all the up-regulated proteins indentified, the mRNA and protein level of galectin-1 was most remarkably changed. Knockdown of galectin-1 partially blocked the differentiation induced by HIF-1αa overexpression in U937T cells as assessed by morphological criteria and differentiation associated-antigens. Notably, reduced expression of C/EBPαa, a critical transcription factor for granulocyte differentiation, could inhibit the up-regulation of galectin-1 induced by HIF-1αa, and inducible expression of C/EBPαa in U937T cells also increased galectin-1 expression. Furthermore, by using the luciferase assay and chromatin immunoprecipitation we localized the binding site of C/EBPαa in the promoter of galectin-1. Finally the role of galectin-1 during chloride-simulated hypoxia and mild hypoxia was addressed by decreasing the expression of galectin-1 with small interfering RNA. Taken together, these results conclude that galectin-1 is required for hypoxia triggered C/EBPαa dependent AML cell differentiation.