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 modulation of cell surface adhesion molecules of acute myelogenous leukemia blast cells is presented. Cytofluorometric studies on fresh blast cells have demonstrated that CD11a, CD11b CD11c, CD15, CD45RO and CD54 expression is significantly lower in acute promyelocytic leukemia (APL) than is acute myeloid leukemia of other subtypes (AML). In vitro treatment with ATRA dramatically modifies the adhesion phenotype of APL blast cells, promoting a consistently striking up-regulation of CD11b, CD11c, CD15, CD65, CD54, and CD38. Which is in general, poorly demonstrable in AML. The behaviour of CD15s is variable and fully independent from CD15 and CD65 in induction experiments, suggesting a differential enzyme regulation within the selectin ligand system. ATRA is capable, in both APL and AML, of producing a switch from the high- (RA) to the low- (RO) molecular weight isoform of CD54, Moreover, treatment with this retinoid exerts a negative regulation of the membrane expression of CD49e, CD58 and CD11a in APL as well as in AML. Of particular interest is the fact that the negative effect on CD1 1a expression generates an asynchronous phenotype in APL (CD11a-, CD11b+, CD15+), undetectable on normal maturing myeloid cells. In the last part of this review the possible implications of adhesion molecule modulation in the pathogenesis of ATRA syndrome are discussed.
Di Noto
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R
Divisione di Oncologia Sperimentale C, Ospedale A. Cardarelli, Naples, Italy.
Lo Pardo
C
C
Schiavone
E M
EM
Ferrara
F
F
Manzo
C
C
Vacca
C
C
Del Vecchio
L
L
D000208:Acute Disease; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000378:metabolism*; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*
D015815:Cell Adhesion Molecules; D014212:Tretinoin