Expression of beta1-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 therefore 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 and to favor their release from the bone marrow into the blood at initiation of therapy. In order to determine whether these effects might be mediated in part by modifications of beta1-integrin and pseudoimmunoglobulin expression on APL cells, the expression of these adhesion molecules on bone marrow (BM) blast cells from 24 APL patients was assayed 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% positive cases (> or = 20% positive cells). Despite a wide variability between individual samples, the expression of beta1-integrins and that of pseudo-immunoglobulins tended to be higher in APL in comparison with that of a cohort of 63 patients with other AML subtypes 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 expression of adhesion molecules. Granulocytic differentiation was marked by persistence of CD15 expression. Antigen expression was decreased after culture with ATRA for all beta1-integrins (except CD49b and CD49f) and pseudoimmunoglobulins (except CD54) tested. However, changes were statistically significant only for CD56 (P=0.04), CD49d (P=0.02) and CD49e (P=0.01). The modifications in the expression of the beta1-integrins and pseudo immunoglobulins were not specific to ATRA-induced differentiation, but commonly observed with differentiation. Furthermore, the modifications in the adhesive properties of APL cells to extracellular matrix proteins, observed on adhesion assays, were not statistically significant after ATRA-induced differentiation. Overall, the level of expression of beta1-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 increase in leukocyte counts observed during the first days of ATRA therapy.
Thomas
X
X
Service d'Hématologie, Hôpital Edouard Herriot, Lyon, France.
Anglaret
B
B
Campos
L
L
Thiebaut
A
A
Sabido
O
O
Bailly
M
M
Archimbaud
E
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis*; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002454:Cell Differentiation; D005260:Female; D006801:Humans; D019012:Integrin beta1 / Q000096:biosynthesis*; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D019012:Integrin beta1