Skip to main content

A Glycomic Approach Towards Identification of Signature Molecules in CD34+ Haematopoietic Stem Cells from Umbilical Cord Blood

  • Chapter
  • First Online:
Book cover Biochemical and Biophysical Roles of Cell Surface Molecules

Abstract

Umbilical cord blood (UCB) is a powerful storehouse for normal CD34+ haematopoietic stem cells (HSCs), often used for allogeneic bone marrow (BM) transplantation in malignant and non-malignant diseases. The glycomic especially the sialoglycomic aspect of these HSCs has been unravelled in this study. Cell surface expression of the glycans with the related enzymatic activities has been compared with the BM of childhood acute lymphoblastic leukaemia, a common BM-associated malignancy. An enhanced cell surface expression of α2,3-linked sialic acid, P- and E-selectins, and intercellular adhesion molecule along with reduced expression of L-selectin distinguishes CD34+ HSCs of UCB from leukaemic samples. More importantly, high expression of O-acetylated sialoglycoproteins, a hallmark of lymphoblasts, is drastically reduced in the CD34+ HSCs of UCB and is substantiated by the low activity of sialylate-O-acetyltransferase and high sialidase activity. In contrast, a significant variation is evident in the expression of sialic acid, α2,6-linked sialic acids, and the sialyltransferase activity. Taken together, these studies indicate a few signature molecules, forming a unique glycomic template, which may be a potential indicator, reassuring the normal profile of these stem cells, to be used for future transplantation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Brown JA, Boussiotis VA (2008) Umbilical cord blood transplantation: basic biology and clinical challenges to immune reconstitution. Clin Immunol 127:286–297

    Article  CAS  Google Scholar 

  • Chowdhury S, Mandal C (2009) O-acetylated sialic acids: multifaceted role in childhood acute lymphoblastic leukaemia. Biotechnol J 4:361–374

    Article  CAS  Google Scholar 

  • Chowdhury S, Bandyopadhyay S, Chandra S, Mandal C (2007) Comparative analysis of differential expression of sialic acids and adhesion molecules on mononuclear cells of bone marrow and peripheral blood in childhood acute lymphoblastic leukaemia at diagnosis and clinical remission. Indian J Biochem Biophys 44:357–365

    CAS  PubMed  Google Scholar 

  • Chowdhury S, Bandyopadhyay S, Mandal C, Chandra S, Mandal C (2008) Flow-cytometric monitoring of disease-associated expression of 9-O-acetylated sialoglycoproteins in combination with known CD antigens, as an index for MRD in children with acute lymphoblastic leukaemia: a two-year longitudinal follow-up study. BMC Cancer 8:40

    Article  Google Scholar 

  • Chowdhury S, Chandra S, Mandal C (2014) 9-O-acetylated sialic acids differentiating normal haematopoietic precursors from leukemic stem cells with high aldehyde dehydrogenase activity in children with acute lymphoblastic leukaemia. Glycoconj J 31(6–7):523–535

    Article  CAS  Google Scholar 

  • George AA, Franklin J, Kerkof K, Shah AJ, Price M, Tsark E, Bockstoce D, Yao D, Hart N, Carcich S, Parkman R, Crooks GM, Weinberg K (2001) Detection of leukemic cells in the CD34(+)CD38(−) bone marrow progenitor population in children with acute lymphoblastic leukemia. Blood 97:3925–3930

    Article  CAS  Google Scholar 

  • Ghosh S, Bandyopadhyay S, Pal S, Das B, Bhattacharya DK, Mandal C (2005a) Increased interferon gamma production by peripheral blood mononuclear cells in response to stimulation of overexpressed disease-specific 9-O-acetylated sialoglycoconjugates in children suffering from acute lymphoblastic leukaemia. Br J Haematol 128:35–41

    Article  CAS  Google Scholar 

  • Ghosh S, Bandyopadhyay S, Mallick A, Pal S, Vlasak R, Bhattacharya DK, Mandal C (2005b) Interferon gamma promotes survival of lymphoblasts overexpressing 9-O-acetylated sialoglycoconjugates in childhood acute lymphoblastic leukaemia (ALL). J Cell Biochem 95:206–216

    Article  CAS  Google Scholar 

  • Ghosh S, Bandyopadhyay S, Mukherjee K, Mallick A, Pal S, Mandal C, Bhattacharya DK, Mandal C (2007) O-acetylation of sialic acids is required for the survival of lymphoblasts in childhood acute lymphoblastic leukemia (ALL). Glycoconj J 24:17–24

    Article  CAS  Google Scholar 

  • Hollands P, McCauley C (2009) Private cord blood banking: current use and clinical future. Stem Cell Rev Rep 5:195–203

    Article  Google Scholar 

  • Hough R, Cooper N, Veys P (2009) Allogeneic haemopoietic stem cell transplantation in children: what alternative donor should we choose when no matched sibling is available? Br J Haematol 147(5):593–613

    Article  Google Scholar 

  • Krause DS, Van Etten RA (2007) Right on target: eradicating leukemic stem cells. Trends Mol Med 13:470–481

    Article  CAS  Google Scholar 

  • Mandal C, Chatterjee M, Sinha D (2000) Investigation of 9-O-acetylated sialoglycoconjugates in childhood acute lymphoblastic leukaemia. Br J Haematol 110:801–812

    Article  CAS  Google Scholar 

  • Mandal C, Srinivasan GV, Chowdhury S, Chandra S, Mandal C, Schauer R, Mandal C (2009) High level of sialate-O-acetyltransferase activity in lymphoblasts of childhood acute lymphoblastic leukaemia (ALL): enzyme characterization and correlation with disease status. Glycoconj J 26:57–73 and references therein

    Article  CAS  Google Scholar 

  • Mandal C, Tringali C, Mondal S, Anastasia L, Chandra S, Venerando B, Mandal C (2010) Down regulation of membrane-bound Neu3 constitutes a new potential marker for childhood acute lymphoblastic leukemia and induces apoptosis suppression of neoplastic cells. Int J Cancer 126(2):337–349

    Article  CAS  Google Scholar 

  • Mondal S, Chandra S, Mandal C (2009) Elevated mRNA level of hST6Gal I and hST3Gal V positively correlates with the high risk of pediatric acute leukemia. Leuk Res 34(4):463–470

    Article  Google Scholar 

  • Mukherjee K, Chowdhury S, Mondal S, Mandal C, Chandra S, Bhadra RK, Mandal C (2007) 9-O-acetylated GD3 triggers programmed cell death in mature erythrocytes. Biochem Biophys Res Commun 362:651–657

    Article  CAS  Google Scholar 

  • Mukherjee K, Chava AK, Mandal C, Dey SN, Kniep B, Chandra S, Mandal C (2008) O-acetylation of GD3 prevents its apoptotic effect and promotes survival of lymphoblasts in childhood acute lymphoblastic leukaemia. J Cell Biochem 105:724–734

    Article  CAS  Google Scholar 

  • Mukherjee K, Chava AK, Bandyopadhyay S, Mallick A, Chandra S, Mandal C (2009) Co-expression of 9-O-acetylated sialoglycoproteins and their binding proteins on lymphoblasts of childhood acute lymphoblastic leukemia: an anti-apoptotic role. Biol Chem 390:325–335

    Article  CAS  Google Scholar 

  • Pal S, Ghosh S, Bandyopadhyay S, Mandal C, Bandhyopadhyay S, Bhattacharya DK, Mandal C (2004) Differential expression of 9-O-acetylated sialoglycoconjugates on leukemic blasts: a potential tool for long-term monitoring of children with acute lymphoblastic leukemia. Int J Cancer 111:270–277

    Article  CAS  Google Scholar 

  • Satomaa T, Heiskanen A, Mikkola M, Olsson C, Blomqvist M, Tiittanen M, Jaatinen T, Aitio O, Olonen A, Helin J, Hiltunen J, Natunen J, Tuuri T, Otonkoski T, Saarinen J, Laine J (2009) The N-glycome of human embryonic stem cells. BMC Cell Biol 10:42 and references therein

    Article  Google Scholar 

  • Schauer R (2000) Achievements and challenges of sialic acid research. Glycoconj J 17:485–499

    Article  CAS  Google Scholar 

  • Sinha D, Mandal C, Bhattacharya DK (1999a) Identification of 9-O acetyl sialoglycoconjugates (9-OAcSGs) as biomarkers in childhood acute lymphoblastic leukaemia using a lectin, AchatininH, as a probe. Leukemia 13:119–125

    Article  CAS  Google Scholar 

  • Sinha D, Mandal C, Bhattacharya DK (1999b) A novel method for prognostic evaluation of childhood acute lymphoblastic leukemia. Leukemia 13:309–312

    Article  CAS  Google Scholar 

  • Storms RW, Green PD, Safford KM, Niedzwiecki D, Cogle CR, Colvin OM, Chao NJ, Rice HE, Smith CA (2005) Distinct hematopoietic progenitor compartments are delineated by the expression of aldehyde dehydrogenase and CD34. Blood 106:95–102

    Article  CAS  Google Scholar 

Download references

Acknowledgement

This work received financial support from the CSIR, New Delhi, Govt. of India. CM sincerely acknowledges the financial support from JC Bose National Fellowship (DST) and Distinguished Biotechnology Research Professor (DBT).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Chitra Mandal .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Chowdhury, S. et al. (2018). A Glycomic Approach Towards Identification of Signature Molecules in CD34+ Haematopoietic Stem Cells from Umbilical Cord Blood. In: Chattopadhyay, K., Basu, S. (eds) Biochemical and Biophysical Roles of Cell Surface Molecules. Advances in Experimental Medicine and Biology, vol 1112. Springer, Singapore. https://doi.org/10.1007/978-981-13-3065-0_21

Download citation

Publish with us

Policies and ethics