The role of galectins in differentiation of acute myeloid leukemia cells
Abstract
Galectins are a family of β-galactoside binding proteins with roles in cellular differentiation, apoptosis, and cancer progression. To better understand this important class of proteins, HL-60 acute myeloid leukemia cells were used as a model for comparative study of the effects of recombinant galectins, galectin inhibitors, and all-trans retinoic acid (ATRA) on granulocytic differentiation. Targeted inhibition of galectin-1 or -3 induced characteristics of neutrophilic differentiation including segmentation of nuclei, upregulation of neutrophil cytosolic factor 1 gene expression, and a global decrease in protein glycosylation with O-linked N-acetylglucosamine. Recombinant galectin-8 or -9 also induced granulocytic differentiation that was not observed with recombinant galectin-1 or -3. However, the galectin induced differentiation was moderate relative to the strong stimulatory effects observed with ATRA. In silico analysis of acute myeloid leukemia data from the Cancer Genome Atlas revealed changes in galectin gene expression profiles related to the various molecular subtypes of acute myeloid leukemia. A ratio of galectin-12/galectin-9 gene expression was identified as a potential diagnostic marker of leukemia subtypes. Correlation analysis between galectin gene pairs revealed changes to the glycobiological landscape and relation to granulocytic differentiation markers in leukemia cells. Among galectin genes, only the increased galectin-1 gene expression was indicative of patient poor prognosis in all acute myeloid leukemia cohorts. These results indicate that while galectins share similar structures, they elicit different responses and display different gene expression patterns in relation to granulocytic differentiation in acute myeloid leukemia. Furthermore, these findings suggest the possible utility of galectins as targets for differential therapeutics.