O-acetylation of sialic acids is required for the survival of lymphoblasts in childhood acute lymphoblastic leukemia (ALL)

Ghosh, Shyamasree ; Bandyopadhyay, Suman ; Mukherjee, Kankana ; Mallick, Asish ; Pal, Santanu ; Mandal, Chhabinath ; Bhattacharya, Dilip K. ; Mandal, Chitra (2007) O-acetylation of sialic acids is required for the survival of lymphoblasts in childhood acute lymphoblastic leukemia (ALL) Glycoconjugate Journal, 24 (1). pp. 17-24. ISSN 0282-0080

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Official URL: http://www.springerlink.com/content/q845w805v5vp11...

Related URL: http://dx.doi.org/10.1007/s10719-006-9007-y


Exploiting the selective affinity of Achatinin-H towards 9-O-acetylneuraminic acid(α2-6)GalNAc, we have demonstrated the presence of 9-O-acetylated sialoglycoproteins (Neu5,9Ac2-GPs) on hematopoietic cells of children suffering from acute lymphoblastic leukemia (ALL), indicative of defective sialylation associated with this disease. The carbohydrate epitope of Neu5,9Ac2-GPsALL was confirmed by using several synthetic sialic acid analogues. They are functionally active signaling molecules as demonstrated by their role in mediating lymphoproliferative responses and consequential increased production of IFN-γ due to specific stimulation of Neu5,9Ac2-GPs on PBMCALL with Achatinin-H. Cells devoid of 9-O-acetylations (9-O-AcSA-) revealed decreased nitric oxide production as compared to 9-O-AcSA+ cells on exposure to IFN-γ. Under this condition, a decrease in viability of 9-O-AcSA- cells as compared to 9-O-AcSA+ cells was also observed which was reflected from increased caspase 3 activity and apoptosis suggesting the protective role of this glycotope. These Neu5, 9Ac2-GPs are also capable of inducing disease-specific anti-Neu5, 9Ac2-GPs antibodies in ALL children. Additionally, we have observed that disease-specific anti-Neu5, 9Ac2-GPs have altered glycosylation profile, and they are incapable of exerting a few Fc-glycosylation-sensitive effector functions. These observations hint toward a disbalanced homeostasis, thereby enabling the cancer cells to escape host defense. Taken together, it may be hypothesized that Neu5, 9Ac2-GPs and their antibodies play a prominent role in promoting the survival of lymphoblasts in ALL.

Item Type:Article
Source:Copyright of this article belongs to Springer-Verlag.
Keywords:Acute Lymphoblastic Leukemia; Achatinin-H: an O-acetylated Sialic Acid Binding Lectin; 9-O-acetylated Sialoglycoconjugates; IFN-γ Caspase-3-like Activity
ID Code:19120
Deposited On:25 Nov 2010 14:17
Last Modified:28 Feb 2011 09:09

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