ERK5 Pathway Regulates Transcription Factors Important for Monocytic Differentiation of Human Myeloid Leukemia Cells

This study was performed using established cell lines HL60 and U937, and primary cultures of blasts from 10 patients with ML. We found that ERK5 and its direct downstream target transcription factor MEF2C are upregulated by 1,25D in parallel with monocytic differentiation. Further, inhibition of ERK5 activity by specific pharmacological agents BIX02189 and XMD8‐92 alters the phenotype of these cells by reducing the abundance of the VDD‐induced surface monocytic marker CD14, and concomitantly increasing surface expression of the general myeloid marker CD11b. Similar results were obtained when the expression of ERK5 was reduced by siRNA or short hairpin (sh) RNA. ERK5 inhibition resulted in an expected decrease in MEF2C activation. We also found that in AML the transcription factor C/EBPβ is positively regulated, while C/EBPα is negatively regulated by ERK5. These findings provide new understanding of dysregulated differentiation in human myeloid leukemia. J. Cell. Physiol. © 2013 Wiley Periodicals, Inc.
Source: Journal of Cellular Physiology - Category: Cytology Authors: Tags: Original Research Article Source Type: research