EXPRESSION OF BETA-1-INTEGRINS AND PSEUDO-IMMUNOGLOBULINS ON ACUTE PROMYELOCYTIC LEUKEMIA-CELLS AND ITS MODIFICATIONS DURING IN-VITRO DIFFERENTIATION

Adhesion molecules are involved in cell-cell interactions and therefor e probably play a role in the differentiation and egress of cells from the bone marrow, which might be potentially important in the biology of acute promyelocytic leukemia (APL). All-trans retinoic acid (ATRA) is known to induce in vitro and in vivo differentiation of APL cells a nd to favor their release from the bone marrow into the blood at initi ation of therapy. In order to determine whether these effects might be mediated in part by modifications of beta 1-integrin and pseudo-immun oglobulin expression on APL cells, the expression of these adhesion mo lecules on bone marrow (BM) blast cells from 24 APL patients was assay ed at diagnosis by an indirect immunofluorescence method. CD49b, CD49d , CD49e, CD49f, CD54, CD58, and CD56 were expressed respectively on 18 %+/-20% (0-66%), 40%+/-31% (0-96%), 48%+/-32% (0-97%), 29%+/-29% (1-94 %), 51%+/-30% (5-98%), 37%+/-24% (1-85%) and 32%+/-31% (0-97%) of APL cells, with respectively 39%, 71%, 79%, 50%, 70%, 70%, and 53% positiv e cases (greater than or equal to 20% positive cells). Despite a wide variability between individual samples, the expression of beta 1-integ rins and that of pseudo-immunoglobulins tended to be higher in APL in comparison with that of a cohort of 63 patients with other AML subtype s with significant differences for CD54 expression (51%+/-30% vs 28%+/ -27%, P=0.006) and CD56 expression (37%+/-24% vs 17%+/-19%, P=0.0003). An in vitro differentiation assay was performed in nine cases. Cells were harvested after 4-7 days of culture and studied for the expressio n of adhesion molecules. Granulocytic differentiation was marked by pe rsistence of CD15 expression. Antigen expression was decreased after c ulture with ATRA for all beta 1-integrins (except CD49b and CD49f) and pseudo-immunoglobulins (except CD54) tested. However, changes were st atistically significant only for CD56 (P=0.04), CD49d (P=0.02) and CD4 9e (P=0.01). The modifications in the expression of the beta 1-integri ns and pseudo immunoglobulins were not specific to ATRA-induced differ entiation, but commonly observed with differentiation. Furthermore, th e modifications in the adhesive properties of APL cells to extracellul ar matrix proteins, observed on adhesion assays, were not statisticall y significant after ATRA-induced differentiation. Overall, the level o f expression of beta 1-integrins and pseudo-immunoglobulins was higher in APL than in other AML subtypes, and appeared modified with induced differentiation. This was not specific of ATRA, but might be involved in the general differentiation phenomenon. The modulation of adhesion molecules does not seem a sufficient requisite for the development of the retinoic acid syndrome, but could nevertheless be part of the inc rease in leukocyte counts observed during the first days of ATRA thera py. (C) 1998 Elsevier Science Ltd. All rights reserved.