Increased Expression of PML Protein in Lymphocytes Induced by Serum from Patients with Severe Aplastic Anemia

PML is essential for multiple apoptotic pathways and has an altered expression in human oncogenesis. However, the role of PML in regulating cell growth and apoptosis in aplastic anemia (AA) is still unclear. To investigate the involvement of PML in the pathogenesis of AA, the expression of PML protein and apoptosis in lymphocytes was measured with immunofluorescent staining after 24 hours incubation with serum of healthy individuals (controls, n=10) and patients with severe AA (SAA, n=10). After incubation with serum from SAA patients, PML protein was overexpressed both in peripheral lymphocytes from a normal donor and in a B cell line established from cells of the same individual. The normal lymphocytes contained a greater proportion of apoptotic cells after incubation with serum from SAA patients than serum from controls, which correlated to the serum-induced expression of PML. In addition, the induction of PML expression and apoptosis in lymphocytes by the serum was partly blocked by caspase 8 inhibitor, whereas no significant difference was found before and after caspase 3 inhibitor was added. These results indicate that some components contain of the serum of SAA patients, which was confirmed to γ-IFN by us, acts on lymphocytes not only to upregulate PML protein, but also to selectively activate caspase 8, causing apoptosis. This disregulation may play an important role in the pathogenesis of lymphocytopenia in aplastic anemia.