In vitro exposure of acute promyelocytic leukemia cells to arsenic trioxide (As sub(2)O sub(3)) induces the solitary expression of CD66c (NCA-50/90), a member of the CEA family

Arsenic trioxide (As sub(2)O sub(3)) is a useful drug for the treatment, of acute promyelocytic leukemia (APL), acting through a complex mechanism involving the induction of apoptosis. We investigated by flow cytometry whether in vitro treatment of APL leukemic cells with As sub(2)O sub(3) determined specific surface membrane changes. Twelve APL bone marrow aspirates were analyzed following 7 days of in vitro treatment with As sub(2)O sub(3) (0.25, 0.5 and 2.5 mu M) with regard to the expression of a series of differentiation antigens. Twelve acute myeloid leukemia (AML) samples of non-APL morphotype were analyzed as controls. Exposure of APL as well as non-APL samples to any concentration of As sub(2)O sub(3) did not affect the expression of beta 2 integrins (CD11a and CD11b), CD45 isoforms (RA, RB and R0), CD44/HCAM, CD33 and the CEA-related antigen family members CD66ade and CD66b, thus failing to disclose any maturating effect. Of interest, in all APL samples (but not in AML) every tested dose of As sub(2)O sub(3) determined a dramatic upregulation of CD66c display: intermediate concentration (0.5 mu M) of As sub(2)O sub(3) increased the median percentage of CD66c sub(+) cells from 5% in control cultures (25th-75th percentile 2-12%) to 80% in drug-exposed cultures (25th-75th percentile 58-90%) (P