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 lymphoblastic leukaemia, ALL (PBMC ALL , 9‐ O ‐AcSA + cells) was demonstrated by using a lectin, Achatinin‐H, whose lectinogenic epitope was 9‐ O ‐AcSAα2‐6GalNAc. Our aim was to evaluate the in vitro contributory role of this glycotope (9‐ O ‐AcSAα2‐6GalNAc) 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 PBMC ALL using O ‐acetyl esterase. An elevated level of serum interferon gamma (IFN‐γ) in affected children led us to think that PBMC ALL are continuously exposed specifically to this cytokine. Accordingly, 9‐ O ‐AcSA + and 9‐ O ‐AcSA − cells were exposed in vitro to IFN‐γ. 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‐γ 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 iNOS in reaction mixture. Therefore, it may be envisaged that a link exists between induction of this glycotope and their role in regulating viability of PBMC ALL . Taken together, it is reasonable to hypothesise that O ‐acetylation of sialic acids on PBMC ALL may be an additional mechanism that promotes the survival of lymphoblasts by avoiding apoptosis via IFN‐γ‐induced NO production. © 2004 Wiley‐Liss, Inc.