In vitro exposure of acute promyelocytic leukemia cells to arsenic trioxide (As2O3) induces the solitary expression of CD66c (NCA-50/90), a member ofthe CEA family

Arsenic trioxide (As2O3) is a useful drug for the treatment of acute promye locytic leukemia (APL), acting through a complex mechanism involving the in duction of apoptosis. We investigated by flow cytometry whether in vitro tr eatment of APL leukemic cells with As2O3 determined specific surface membra ne changes. Twelve APL bone marrow aspirates were analyzed following 7 days of in vitro treatment with As2O3 (0.25, 0.5 and 2.5 mu M) with regard to t he expression of a series of differentiation antigens. Twelve acute myeloid leukemia (AML) samples of non-APL morphotype were analyzed as controls. Ex posure of APL as well as non-APL samples to any concentration of As2O3 did not affect the expression of beta 2 integrins (CD11a and CD11b), CD45 isofo rms (RA, RE and RO), CD44/H-CAM, CD33 and the CEA-related antigen family me mbers CD66ade and CD66b, thus failing to disclose any maturating effect. Of interest, in ail APL samples (but not in AML) every tested dose of As2O3 d etermined a dramatic upregulation of CD66c display: intermediate concentrat ion (0.5 mu M) Of As2O3 increased the median percentage of CD66c(+) cells f rom 5% in control cultures (25th-75th percentile 2-12%) to 80% in drug-expo sed cultures (25th-75th percentile 58-90%) (P<0.001). The induction of soli tary expression of CD66c is a new finding which demonstrates As2O3 capabili ty of generating phenotypic changes absolutely restricted to APL cells. Mor eover, these results provide experimental basis for considering the involve ment of the newly described CD66 signalling pathway in As2O3-driven program med cell death.