Journal
GLYCOCONJUGATE JOURNAL
Volume 24, Issue 1, Pages 17-24Publisher
SPRINGER
DOI: 10.1007/s10719-006-9007-y
Keywords
acute lymphoblastic leukemia; achatinin-H; an O-acetylated sialic acid binding lectin; 9-O-acetylated sialoglycoconjugates; IFN-gamma; caspase-3-like activity
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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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