All-trans retinoic acid promotes a differential regulation of adhesion molecules on acute myeloid leukaemia blast cells.
In the present study we investigated the membrane expression of selectin ligands (CD15/Le(x), CDw65/VIM2, CD15s/sLe(x), beta 2 integrins (CD11a/LFA-1, CD11b/Mac-1) and CD45 phosphatase isoforms (CD45RA, CD45O) 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 molecules. Furthermore, it was able to exert effects specific for acute promyelocytic leukaemia (APL) blast cells, as well as to induce a series of non-cytotype-restricted phenotypic changes. An impressive feature of ATRA induction was a simultaneous increase in the expression of CD15, CDw65 and CD11b on leukaemic promyelocytes. The sialylated antigen CD15s, however, showed results independent from the other two carbohydrates (CD15 and CDw65), suggesting a differential enzymatic regulation within the selectin ligands system. In spite of the well-recognized expression of CD11a throughout all stages of normal myeloid differentiation, 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 constitutively expressing this antigen. In APL cases ATRA generated an asynchronous phenotype (CD15+, CDw65+, CD11b+, CD11a-), undetectable on normally maturing myeloid cells, but consistent with the concept that incomplete differentiation, in terms of surface molecule expression, can be sufficient to obtain therapeutic results.
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Divisione di Oncologia Sperimentale C, Istituto Nazionale dei Tumori di Napoli, Italy.
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Ferrara
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Manzo
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Lo Pardo
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D000208:Acute Disease; D015703:Antigens, CD / Q000187:drug effects; D018845:CD11 Antigens / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000187:drug effects* / Q000378:metabolism; D002454:Cell Differentiation; D006801:Humans; D007951:Leukemia, Myeloid / Q000378:metabolism*; D016256:Lewis X Antigen / Q000187:drug effects; D009363:Neoplasm Proteins / Q000187:drug effects*; D014212:Tretinoin / Q000494:pharmacology*
D015703:Antigens, CD; D018845:CD11 Antigens; D015815:Cell Adhesion Molecules; D016256:Lewis X Antigen; D009363:Neoplasm Proteins; D014212:Tretinoin