Background and Objectives Differentiation Syndrome (DS) is a treatment complication which can occur flex 4 heartworm test in patients treated with acute promyelocytic leukemia (APL) with all transretinoic acid (ATRA) or As2O3, and is characterized by enhanced leukocyte transmigration.As2O3, Phenylbutyrate (PB) and G-CSF are known to potentiate ATRA effects.Our aim was to analyze the changes in expression and function of adhesion molecules induced by ATRA, As2O3, G-CSF and PB, and their association.
Design and Methods APL blasts and NB4 cells were treated with ATRA, As2O3, PB, G-CSF or their association and the expression of adhesion molecules was determined by flow cytometry.Cell adhesion was evaluated in vitro using Matrigel and for the in vivo analysis, Balb-c mice were injected with NB4 cells pre-treated with ATRA, As2O3, ATRA+G-CSF or ATRA+As2O3.In addition, CD54 and CD18 knock-out mice were injected with NB4 cells kicker pro comp 10 and concomitantly treated with ATRA.
In both models, the MPO activity in the lungs was determined 6 hours after the injection of the cells.Results In NB4 and APL blasts, ATRA and As2O3 increased CD54 expression, but no synergism was detected.CD11b and CD18 were also up-regulated by ATRA in primary cells.
PB and G-CSF had no effect, but the latter potentiated ATRA-induced CD18 up-regulation.These changes were accompanied by increased adhesion to Matrigel and to lung microvasculature, and reversed by anti-CD54, anti-CD18 antibodies.In CD54 and CD18 knock-out mice the ATRA effect was canceled.
Interpretation and Conclusions The use of As2O3, PB and G-CSF in association with ATRA should not aggravate DS in APL.