FAS-MEDIATED APOPTOSIS WITH NORMAL EXPRESSION OF BCL-2 AND P53 IN LYMPHOCYTES FROM APLASTIC-ANEMIA

In order to investigate the involvement of apoptosis in the pathogenes is of aplastic anaemia (AA) we measured the expression of the Fas rece ptor (membrane protein that triggers apoptosis), Fas ligand (Fast), bc l-2 (cytoplasmatic protein that blocks apoptosis) and p53 (nuclear pro tein that induces apoptosis) in CD3 and CD19 lymphocytes from the peri pheral blood or bone marrow of controls, patients with AA, aplastic an aemia in complete remission (AA-CR) and multiply transfused patients w ithout aplastic anaemia. The Fas receptor was overexpressed in both T and B lymphocytes from the peripheral blood and bone marrow from patie nts with AA, These abnormalities were not detected in AA-CR or multipl y transfused patients.' CD3/FasL cells were not increased and no Fast expression was detected in B lymphocytes. Bcl-2 was highly expressed i n lymphocytes from controls, AA, AA-CR and multiply transfused patient s (> 99% of positive cells) whereas p53 was not detected in any group. To further characterize the functional activity of the Fas receptor w e performed a Fas-induced apoptosis assay in peripheral blood lymphocy tes using an anti-Fas monoclonal antibody The crosslinking of the Fas receptor transduced an increased apoptotic signal in lymphocytes from AA patients, but not in lymphocytes from controls, AA-CR patients or m ultiply transfused patients. Taken together, these data suggest that a Fas-based mediated apoptosis without the apparent participation of bc l-2 or p53 is a possible mechanism of lymphocyte depletion in patients with AA. In addition, these findings suggest that Fas expression is a continuous event occurring from progenitor bone marrow cells to matur e cells.