Increased interferon gamma production by peripheral blood mononuclear cells in response to stimulation of overexpressed disease-specific 9-O-acetylated sialoglycoconjugates in children suffering from acute lymphoblastic leukaemia

Abstract

Disease-specific over-expression of 9-O-acetylated sialoglycoconjugates (9-O-AcSGs) on peripheral blood mononuclear cells (PBMC) of children with acute lymphoblastic leukaemia (ALL, PBMC(ALL)) has been demonstrated using a lectin, Achatinin-H, with specificity towards 9-O-AcSAalpha2-6GalNAc. This study investigated the contributory role of 9-O-AcSGs induced on PBMC(ALL). Stimulation of PBMC(ALL) with Achatinin-H through 9-O-AcSGs led to a lymphoproliferative response with a significantly increased interferon-gamma (IFN-gamma) production when compared with unstimulated cells as demonstrated by enzyme-linked immunosorbent assay and mRNA expression. Under identical conditions, PBMC(ALL) ablated of O-acetylations did not respond to such stimulation. In summary, it may be concluded that stimulation of over-expressed 9-O-AcSGs regulate signalling for proliferation, leading to the release of IFN-gamma. Controlled expression of these molecules may be exploited as potential targets for therapy, promising beneficial effects to children with ALL.