O-acetylation of sialic acids is required for the survival of lymphoblasts in childhood acute lymphoblastic leukemia (ALL)
Metadata of CSIR Papers
View Archive Info| Field | Value | |
| Title |
O-acetylation of sialic acids is required for the survival of lymphoblasts in childhood acute lymphoblastic leukemia (ALL)
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| Creator |
Ghosh, S
Bandyopadhyay, S Mukherjee, K Mallick, A Pal, S Mandal, C Bhattacharya, DK Mandal, C |
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| Subject |
Biochemistry & Molecular Biology
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| Description |
Exploiting the selective affinity of Achatinin-H towards 9-O-acetylneuraminic acid(alpha 2-6)GalNAc, we have demonstrated the presence of 9-O-acetylated sialoglycoproteins (Neu5,9Ac(2)-GPs) on hematopoietic cells of children suffering from acute lymphoblastic leukemia (ALL), indicative of defective sialylation associated with this disease. The carbohydrate epitope of Neu5,9Ac(2)-GPs(ALL) 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-gamma due to specific stimulation of Neu5,9Ac(2)-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-gamma. 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 Neu5,9Ac(2)-GPs are also capable of inducing disease-specific anti-Neu5,9Ac(2)-GPs antibodies in ALL children. Additionally, we have observed that disease-specific anti-Neu5,9Ac(2)-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 Neu5,9Ac(2)-GPs and their antibodies play a prominent role in promoting the survival of lymphoblasts in ALL.
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| Publisher |
SPRINGERDORDRECHTVAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
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| Date |
2011-09-20T12:12:42Z
2011-09-20T12:12:42Z 2007 |
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| Type |
Proceedings Paper
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| Identifier |
GLYCOCONJUGATE JOURNAL
0282-0080 http://hdl.handle.net/123456789/14388 |
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| Language |
English
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