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Inhibiting the platelet derived growth factor receptor increases signs of retinoic acid syndrome in myeloid differentiated HL‐60 cells
Author(s) -
Reiterer Gudrun,
Bunaciu Rodica P.,
Smith James L.,
Yen Andrew
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.06.016
Subject(s) - acute promyelocytic leukemia , myeloid leukemia , retinoic acid , cancer research , integrin alpha m , chemistry , integrin , myeloid , receptor , endocrinology , medicine , microbiology and biotechnology , biology , biochemistry , gene
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.