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Interferon Gamma Promotes Survival of Lymphoblasts Overexpressing 9-O-Acetylated Sialoglycoconjugates in Childhood Acute Lymphoblastic Leukaemia (ALL)

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Title Interferon Gamma Promotes Survival of Lymphoblasts
Overexpressing 9-O-Acetylated Sialoglycoconjugates
in Childhood Acute Lymphoblastic Leukaemia (ALL)
 
Creator Ghosh, Shyamasree
Bandyopadhyay, Suman
Mallick, Asish
Pal, Santanu
Vlasak, Reinhard
Bhattacharya, Dilip K
Mandal, Chitra
 
Subject Drug Development/Diagnostics & Biotechnology
 
Description 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 (PBMCALL, 9-O-AcSAþ cells) was demonstrated by using a lectin, Achatinin-H, whose lectinogenic epitope was 9-O-AcSAa2-6GalNAc. Our aim was to evaluate the in vitro
contributory role of this glycotope (9-O-AcSAa2-6GalNAc) towards the survival of these 9-O-AcSAþ 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-g) in affected children led us to think that PBMCALL are continuously exposed specifically to this cytokine. Accordingly, 9-O-AcSAþ and 9-O-AcSA� cells were exposed in vitro to IFN-g. A twofold increasedNOrelease along with inducibleNOsynthase (iNOS)mRNAexpression by the 9-O-AcSAþ cells was observed as compared to the 9-O-AcSA� cells. The decreased viability of IFN-g exposed 9-OAcSA � cells as compared to 9-O-AcSAþ 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 PBMCALL. Taken together, it is reasonable to hypothesise thatO-acetylation of sialic acids on
PBMCALL may be an additional mechanism that promotes the survival of lymphoblasts by avoiding apoptosis via IFN-ginduced NO production.
 
Date 2005
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1125/1/JOURNAL_OF_CELLULAR_BIOCHEMISTRY_%2C__95_(_1)%2C__206%2D216__[64].pdf
Ghosh, Shyamasree and Bandyopadhyay, Suman and Mallick, Asish and Pal, Santanu and Vlasak, Reinhard and Bhattacharya, Dilip K and Mandal, Chitra (2005) Interferon Gamma Promotes Survival of Lymphoblasts Overexpressing 9-O-Acetylated Sialoglycoconjugates in Childhood Acute Lymphoblastic Leukaemia (ALL). Journal of Cellular Biochemistry, 95 (1). pp. 206-216.
 
Relation http://dx.doi.org/10.1002/jcb.20382
http://www.eprints.iicb.res.in/1125/