Abstract
Differentiation therapy can supplement the therapy of APL, but other subtypes of AML are treated principally with cytotoxic agents, with few lasting remissions. While the induction of monocyte followed by macrophage differentiation by vitamin D derivatives (VDDs) is dramatic in cultured AML cells of all subtypes, attempts to translate this to the clinic have not been effective. Thus, better understanding of the mechanisms underlying VDD-induced differentiation may improve this approach. The key events in this form of differentiation include increased expression of CD11b, and the transcription factor PU.1 is known to be a part of this process. We show here that in the transition of monocytes to macrophages induced by a VDD, ERK5, a member of the MAPK family of signaling molecules, prevents PU.1 expression. However, upon ERK5 inhibition PU.1 protein is stabilized by HSP70.Thus, ERK5 may be a target for manipulation of the immunoregulatory actions of macrophages in cancer.
Acknowledgments
We thank Dr. Xuening Wang for the helpful discussions and technical help. This study was supported by NJCCR Postdoctoral Fellowship grant #DFHS15PPC024 to RZ, and R01 CA044722-26 from NCI to GPS.
Potential conflict of interest
Disclosure forms provided by the authors are available with the full text of this article online at http://dx.doi.org/10.1080/10428194.2016.1243675.