Interferon gamma promotes survival of lymphoblasts overexpressing 9-O-acetylated sialoglycoconjugates in childhood acute lymphoblastic leukaemia (ALL)

An enhanced linkage-specific 9-O-acetylated sialic acid (9-O-AcSA) on peripheral blood mononuclear cells (PBMC) of children with acute lyrnphoblastic leukaemia, ALL (PBMCALL, 9-O-AcSA(+) cells) was demonstrated by using a lectin, Achatinin-H, whose lectinogenic epitope was 9-O-AcSA alpha 2-6GalNAc. Our aim was to evaluate the in vitro contributory role of this glycotope (9-O-AcSA alpha 2-6GalNAc) towards the survival of these 9-O-AcSA(+) cells in ALL-patients. For direct comparison, 9-O-AcSA(-) cells were generated by removing O-acetyl group of 9-O-AcSA present on PBMCALL using O-acetyl esterase. An elevated level of serum interferon gamma (IFN-gamma) in affected children led us to think that PBMCALL are continuously exposed specifically to this cytokine. Accordingly, 9-O-AcSA(+) and 9-O-AcSA(-) cells were exposed in vitro to IFN-gamma. A twofold increased NO release along with inducible NO synthase(iNOS) mRNA expression by the 9-O-AcSA(+) cells was observed as compared to the 9-O-AcSA(-) cells. The decreased viability of IFN-gamma exposed 9-O-AcSA(-) cells as compared to 9-O-AcSA(+) cells were reflected from a 5.0-fold increased caspase-3-like activity and a 10.0-fold increased apoptosis in the 9-O-AcSA(-) cells when production of NO was lowered by adding competitive inhibitor of NOS in reaction mixture. Therefore, it may be envisaged that a link exists between induction of this glycotope and their role in regulating viability of PBMCALL. Taken together, it is reasonable to hypothesise that O-acetylation of sialic acids on PBMCALL may be an additional mechanism that promotes the survival of lymphoblasts by avoiding apoptosis via IFN-gamma-induced NO production. (c) 2005 Wiley-Liss, Inc.