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

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Abstract

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.

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Abbreviations

ALL:

Acute Lymphoblastic Leukemia

IFN-γ:

interferon gamma

9-O-AcSA:

9-O-acetylated sialic acids

9-O-acetylated sialoglycoproteins:

Neu5,9Ac2-GPs

de-O-acetylated cells:

9-O-AcSA−

PBMCALL :

Peripheral blood mononuclear cells from ALL patients

NO:

nitric oxide

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Acknowledgment

This work was supported by the Department of Science and Technology and Indian Council of Medical Research, Council of Scientific and Industrial Research, Goverment of India. Our sincere thanks to Dr. R. Vlasak, Applied BioTechnology, University of Salzburg, Austria for providing O-acetyl esterase and Prof. Dr. R. Schauer Biochemisches Institut, Christian-Albrechts-Universität zu Kiel, Germany, for fluorimetric HPLC, and Prof. R. Brossmer, Biochemistry Center, Universität Heidelberg, Germany, for providing synthetic sialic acid analogues.

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Authors and Affiliations

  1. Immunobiology Division, Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata, 700 032, India

    Shyamasree Ghosh, Suman Bandyopadhyay, Kankana Mukherjee, Asish Mallick, Santanu Pal & Chitra Mandal

  2. Vivekananda Institute of Medical Sciences, Kolkata, 700045, India

    Dilip K. Bhattacharya

  3. Drug Design Development and Molecular Modelling, Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata, 700 032, India

    Chhabinath Mandal

Authors
  1. Shyamasree Ghosh
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  2. Suman Bandyopadhyay
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  3. Kankana Mukherjee
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  4. Asish Mallick
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  5. Santanu Pal
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  6. Chhabinath Mandal
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  7. Dilip K. Bhattacharya
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  8. Chitra Mandal
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Correspondence to Chitra Mandal.

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Ghosh, S., Bandyopadhyay, S., Mukherjee, K. et al. O-acetylation of sialic acids is required for the survival of lymphoblasts in childhood acute lymphoblastic leukemia (ALL). Glycoconj J 24, 17–24 (2007). https://doi.org/10.1007/s10719-006-9007-y

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