Abstract
The clinical activities of all-trans retinoic acid in the treatment of acute promyelocytic leukemia, a unique subtype of acute myeloid leukemia, have triggered extensive studies aimed at defining the mechanisms by which this compound induces differentiation of leukemic cells. Recent studies show that hypoxia-inducible factor-1 alpha (HIF-1 alpha) contributes to the differentiation of acute myeloid leukemia cells via transcriptional activity-independent mechanisms. We investigated whether all-trans retinoic acid affects HIF-1 alpha protein and whether this has a role in all-trans retinoic acid-induced differentiation. The acute myeloid leukemia cell lines NB4 and U937 were treated with all-trans retinoic acid, and HIF-1 alpha/HIF-1 beta mRNA and proteins were measured respectively by real-time quantitative reverse transcriptase polymerase chain reaction and western blotting. To investigate the role of HIF-1 alpha in all-trans retinoic acid-induced differentiation, NB4 cells, U937 cells, U937 cells in which HIF-1 alpha was induced by the withdrawal of tetracycline and U937 cells with stable expression of specific short hairpin RNA against HIF-1 alpha, Runx1, C/EBP alpha and PU.1, were treated with all-trans retinoic acid and/or t...Continue Reading
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