ALL-TRANS-RETINOIC ACID (ATRA) AND THE REGULATION OF ADHESION MOLECULES IN ACUTE MYELOID-LEUKEMIA

A review of recent information on the expression and the ATRA-driven m odulation of cell surface adhesion molecules of acute myelogenous leuk emia blast cells is presented. Cytofluorometric studies on fresh blast cells have demonstrated that CD11a, CD11b, CD11c, CD15, CD45RO and CD 54 expression is significantly lower in acute promyelocytic leukemia ( APL) than in acute myeloid leukemia of other subtypes (AML). In vitro treatment with ATRA dramatically modifies the adhesion phenotype of AP L blast cells, promoting a consistently striking up-regulation of CD11 b, CD11c, CD15, CD65, CD54 and CD38. Which is, in general, poorly demo nstrable in AML. The behaviour of CD15s is variable and fully independ ent from CD15 and CD65 in induction experiments, suggesting a differen tial enzymatic regulation within the selectin ligand system. ATRA is c apable, in both APL and AML, of producing a switch from the high- (RA) to the low- (RO) molecular weight isoform of CD45. Moreover, treatmen t with this retinoid exerts a negative regulation of the membrane expr ession of CD49e, CD58 and CD11a in APL as well as in AML. Of particula r interest is the fact that the negative effect on CD11a expression ge nerates an asynchronous phenotype in APL (CD11a-, CD11b+, CD15+), unde tectable on normal maturing myeloid cells. In the last part of this re view the possible implications of adhesion molecule modulation in the pathogenesis of ATRA syndrome are discussed.