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

✍ Scribed by Shyamasree Ghosh; Suman Bandyopadhyay; Asish Mallick; Santanu Pal; Reinhard Vlasak; Dilip K. Bhattacharya; Chitra Mandal

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 234 KB
• Volume: 95
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.20382

✦ Synopsis

Abstract

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.