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

Reiterer, Gudrun; Bunaciu, Rodica P.; Smith, James L.; Yen, Andrew

doi:10.1016/j.febslet.2008.06.016

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Volume 582, Issue 17 , Pages 2508-2514, 23 July 2008

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

Edited by Veli-Pekka Lehto

Department of Biomedical Sciences, Cornell University, Tower Road, T4008 Veterinary Research Tower, Ithaca, NY 14853, United States

Received 30 April 2008; received in revised form 13 May 2008; accepted 10 June 2008. published online 19 June 2008.

Abstract

PDGFR inhibitors are successfully used in a number of cancer treatments. The standard treatment for acute promyelocytic leukemia (APL) involves differentiation therapy with retinoic acid (RA). However, the relapse rates are significant. In the present work we evaluated the effects of RA therapy in the presence of PDGFR inhibitor, AG1296. Adding AG1296 with RA increased secretion of TNF-α, 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 differentiation markers CD11b, inducible oxidative metabolism and PDGFR-β phosphorylation. While the neutrophil–endothelial cell interactions are strengthened by the combined treatment, the endothelium-substratum interactions are weakened, a situation common in RAS.

Keywords: Leukemia, Integrin, Cytokine, MMP-9, Endothelial cell, RAS