Expression and ATRA-driven modulation of adhesion molecules in acute promyelocytic leukemia.
On fresh leukemic cells taken from 30 patients with acute promyelocytic leukemia (APL) the membrane expression of a series of adhesion molecules including beta 2 integrins (CD11a/LFA-1, CD11b/Mac-1), selectin ligands (CD15/Le(x), CD15s/sLex) and tyrosine-phosphatase isoforms (CD45RA, CD45R0) was analyzed. The expression of these molecules was also studied in nine of these patients following the APL cells' culture with and without all-trans retinoic acid (ATRA). The fresh APL promyelocytes expressed CD45RA and CD15s on their surface, while CD11a, CD11b, CD15, and CD45R0 were constantly absent. In vitro treatment with ATRA consistently increased the expression of CD15, CD11b, and CD45R0 on leukemic promyelocytes; these changes were paralleled by a decrease of CD45RA display. The expression of sialylated antigen CD15s was fully independent from CD15 suggesting a differential enzymatic regulation within this selectin ligand system. ATRA was, however, incapable of promoting the up-regulation of CD11a in APL. As a result, asynchronous phenotype (CD11a-, CD11b+, CD15+, CD15s+/-, CD45RA-, CD45R0+) was generated that is normally undetectable on maturing myeloid cells. In order to provide a further control a case of acute agranulocytosis was also investigated, in which > 75% bone marrow cells were arrested at the promyelocyte stage; these bone marrow cells showed a surface phenotype identical to non-leukemic promyelocytes (CD11a+, CD11b+, CD15+, CD45R0+, CD45RA-) with a spontaneous ability to differentiate in vivo towards the more mature stages of myeloid differentiation. We therefore suggest that in fresh and ATRA-induced APL cells distinct, regular phenotypic changes are identifiable that are probably associated with t(15;17) and not seen in normal and activated bone marrow.
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Divisione di Oncologia Sperimentale C, Immunologia, Istituto Nazionale dei Tumori di Napoli, Italy.
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Ferrara
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Lo Pardo
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Del Vecchio
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D001853:Bone Marrow / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D005434:Flow Cytometry; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000378:metabolism*; D010641:Phenotype; D014212:Tretinoin / Q000494:pharmacology*
D015815:Cell Adhesion Molecules; D014212:Tretinoin