Inhibiting the platelet derived growth factor receptor increases signs of retinoic acid syndrome in myeloid differentiated HL-60 cells

PDGFR inhibitors are successfully used in a number of cancer treatments. The standard treatment for acute promyelocytic leukemia ( APL) involves di. erentiation therapy with retinoic acid ( RA). However, the relapse rates are signi. cant. In the present work we evaluated the e. ects of RA therapy in the presence of PDGFR inhibitor, AG1296. Adding AG1296 with RA increased secretion of TNF- a, IL- 8, and MMP- 9 expression. This treatment induced higher levels of ICAM- 1 endothelial cell expression, and increased cellular mobility. Inhibiting PDGFR enhanced RA- induced expression of integrin. Integrin ligand increased di. erentiation markers CD11b, inducible oxidative metabolism and PDGFR- b phosphorylation. While the neutrophil - endothelial cell interactions are strengthened by the combined treatment, the endothelium- substratum interactions are weakened, a situation common in RAS. (c) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.