THE EFFECT OF DEXAMETHASONE ON FUNCTIONAL-PROPERTIES OF HL-60 CELLS DURING ALL-TRANS-RETINOIC ACID-INDUCED DIFFERENTIATION - ARE THERE IMPLICATIONS FOR THE RETINOIC ACID SYNDROME

Differentiation therapy for acute promyelocytic leukemia (APL) using a ll-trans-retinoic acid (ATRA) has improved the prognosis of the diseas e, ATRA therapy also causes a newly recognized clinical syndrome, the ''retinoic acid syndrome'' (RAS), which can be successfully managed wi th dexamethasone. Because aberrant function of maturing leukemic granu locytes may cause this syndrome, and because dexamethasone is useful c linically, we studied functional properties of maturing HL60 cells cul tured in the presence and absence of dexamethasone, HL60 cells were cu ltured for 4 days with ATRA and studied daily to determine acquisition of mature neutrophil-like properties including phagocytosis, NET redu ction, actin polymerization, chemotaxis and adhesion molecule expressi on. Undifferentated HL60 cells could not polymerize actin or reduce NE T, and exhibited only a minimal abilty to undergo chemotaxis or ingest latex beads, Following 4 days of maturation with ATRA, the cells woul d increase F-actin content in response to interleukin-8, ingest latex beads, migrate in a chemotaxis chamber, reduce NET, and express CD11b, When dexamethasone was added to the cells in culture, there was no ma jor enhancement or suppression of these properties. We also studied th e effect of dexamethasone on functional properties of normal neutrophi ls and found minimal if any effect on their function. Overall, these s tudies suggest that in vitro, dexamethasone has little effect on the f unction of leukemic and normal granulocytes. To further investigate th e pathophysiology of the retinoic acid syndrome, future studies may ne ed to use endothelial cells, cytokines, or granulocytes obtained from APL patients.