Expression of Death Receptors and Associated Regulatory Proteins in Pediatric Acute Lymphoblastic Leukemia: Preliminary Results

Abstract

Altered regulation of the cell cycle and/or apoptosis are well established events in the process of neoplastic transformation. Fas-mediated apoptosis is regulated by several inhibitory proteins in normal lymphocytes and leukemic cells. Some of these protein molecules may also play a role in the induction of apoptosis through death receptors for a similar molecule, TNF-related apoptosis inducing ligand (TRAIL). The involvement of these anti-apoptotic molecules in leukemogenesis is uncertain. Our preliminary findings indicate decreased expression of pro-apoptotic TRAIL-DR4 receptors in leukemic T cells relative to untransformed T cells. This decrease in expression may represent a potential determinant of poor acute lymphoblastic leukemia (ALL) prognosis, as it may result in a favorable biological situation for escape from apoptosis. Our data also demonstrate decreased levels of expression of pro-apoptotic Fas protein molecules in pediatric patient samples, relative to ALL cell lines. This difference suggests that circulating leukemic cells differ in their susceptibility to Fas-mediated apoptosis. Taken together, our data suggest that ALL cell lines and circulating leukemic cells from pediatric patients possess different regulatory mechanisms in order to attenuate Fas-mediated signaling