ALL-TRANS-RETINOIC ACID PROMOTES A DIFFERENTIAL REGULATION OF ADHESION MOLECULES ON ACUTE MYELOID-LEUKEMIA BLAST CELLS

In the present study we investigated the membrane expression of select in ligands (CD15/Le(x), CDw65/VIM2, CD15s/sLe(x)), beta 2 integrins (C D11a/LFA-1, CD11b/Mac-1) and CD45 phosphatase isoforms (CD45RA, CD45RO ) on leukaemic cells from 28 patients with acute myeloid malignancies cultured with and without all-trans retinoic acid (ATRA). Within each adhesion system, ATRA was able to differentially regulate distinct mol ecules. Furthermore, it was able to exert effects specific for acute p romyelocytic leukaemia (APL) blast cells, as well as to induce a serie s of non-cytotype-restricted phenotypic changes. An impressive feature of ATRA induction was a simultaneous increase in the expression of CD 15, CDw65 and CD11b on leukaemic promyelocytes. The sialylated antigen CD15s, however, showed results independent from the other two carbohy drates (CD15 and CDw65), suggesting a differential enzymatic regulatio n within the selectin ligands system. In spite of the well-recognized expression of CD11a throughout all stages of normal myeloid differenti ation, APL blast cells were found to virtually lack LFA-1 expression. Moreover, ATRA was unable to promote an up-regulation of this antigen in APL, while inducing a frequent down-modulation in non-APL cases con stitutively expressing this antigen. In APL cases ATRA generated an as ynchronous phenotype (CD15(+), CDw65(+), CD11b(+), CD11a(-)), undetect able on normally maturing myeloid cells, but consistent with the conce pt that incomplete differentiation, in terms of surface molecule expre ssion, can be sufficient to obtain therapeutic results.