Skip to main content
SpringerLink
Log in

9-O-acetylated sialic acids differentiating normal haematopoietic precursors from leukemic stem cells with high aldehyde dehydrogenase activity in children with acute lymphoblastic leukaemia

  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

Abstract

Childhood acute lymphoblastic leukaemia (ALL) originates from mutations in haematopoietic progenitor cells (HPCs). For high-risk patients, treated with intensified post-remission chemotherapy, haematopoietic stem cell (HSC) transplantation is considered. Autologous HSC transplantation needs improvisation till date. Previous studies established enhanced disease-associated expression of 9-O-acetylated sialoglycoproteins (Neu5,9Ac2-GPs) on lymphoblasts of these patients at diagnosis, followed by its decrease with clinical remission and reappearance with relapse. Based on this differential expression of Neu5,9Ac2-GPs, identification of a normal HPC population was targeted from patients at diagnosis. This study identifies two distinct haematopoietic progenitor populations from bone marrow of diagnostic ALL patients, exploring the differential expression of Neu5,9Ac2-GPs with stem cell (CD34, CD90, CD117, CD133), haematopoietic (CD45), lineage-commitment (CD38) antigens and cytosolic aldehyde dehydrogenase (ALDH). Normal haematopoietic progenitor cells (ALDH+SSCloCD45hiNeu5,9Ac2 -GPsloCD34+CD38−CD90+CD117+CD133+) differentiated into morphologically different, lineage-specific colonies, being crucial for autologous HSC transplantation while leukemic stem cells (ALDH+SSCloCD45loNeu5,9Ac2 -GPshiCD34+CD38+CD90−CD117−CD133−) lacking this ability can be potential targets for minimal residual disease detection and drug-targeted immunotherapy.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Pui, C.H., Campana, D., Evans, W.E.: Childhood acute lymphoblastic leukaemia–current status and future perspectives. Lancet Oncol. 2, 597–607 (2001). doi:10.1016/S1470-2045(01)00516-2

    Article  PubMed  CAS  Google Scholar 

  2. Pui, C.H., Robison, L.L., Look, A.T.: Acute lymphoblastic leukaemia. Lancet 371, 1030–1043 (2008). 10.1016/S0140-6736(08)60457-2

    Article  PubMed  CAS  Google Scholar 

  3. Sallan, S.E.: Myths and lessons from the adult/pediatric interface in acute lymphoblastic leukemia. Hematol. Am. Soc. Hematol. Educ. Program. 128–132 (2006). doi:10.1182/asheducation-2006.1.128

  4. Xu, J., Zhou, T., Zhang, Y.: Role of dendritic cells and chemokines in acute graft-versus-host disease. Front. Biosci. 13, 2065–2074 (2008). 10.2741/2824

    Article  PubMed  CAS  Google Scholar 

  5. Schauer, R.: The diversity of sialic acids and their interplay with lectins. Glycobiology 8, 136–149 (2006)

    Google Scholar 

  6. Ghosh, S., Bandyopadhyay, S., Mukherjee, K., Mallick, A., Pal, S., Mandal, C., 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). doi:10.1007/s10719-006-9007-y

    Article  PubMed  CAS  Google Scholar 

  7. Mandal, C., Schwartz-Albiez, R., Vlasak, R.: Functions and biosynthesis of o-acetylated sialic acids. Top. Curr. Chem. (2012). doi:10.1007/128_2011_310

    PubMed  Google Scholar 

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

  9. Sen, G., Mandal, C.: The specificity of the binding site of Achatinin H, a sialic acid-binding lectin from Achatina fulica. Carbohydr. Res. 268, 115–125 (1995). 10.1016/0008-6215(94)00311-3

    Article  PubMed  CAS  Google Scholar 

  10. Basu, S., Mandal, C., Allen, A.K.: Chemical-modification studies of a unique sialic acid-binding lectin from the snail Achatina fulica. Involvement of tryptophan and histidine residues in biological activity. Biochem. J. 254, 195–202 (1988)

    PubMed  CAS  PubMed Central  Google Scholar 

  11. Mandal, C., Basu, S., Mandal, C.: Physiochemical studies on achatininH, a novel sialic acid-binding lectin. Biochem. J. 257, 65–71 (1989)

    PubMed  CAS  PubMed Central  Google Scholar 

  12. Sinha, D., Mandal, C., Bhattacharya, D.K.: Identification of 9-O acetyl sialoglycoconjugates (9-OAcSGs) as biomarkers in childhood acute lymphoblastic leukemia using a lectin, Achatinin H, as a probe. Leukemia 13, 119–125 (1999)

  13. Mandal, C., Chatterjee, M., Sinha, D.: Investigation of 9-O-acetylated sialoglycoconjugates in childhood acute lymphoblastic leukaemia. Br. J. Haematol. 110, 801–812 (2000). doi:10.1046/j.1365-2141.2000.02105.x

    Article  PubMed  CAS  Google Scholar 

  14. Sinha, D., Mandal, C., Bhattacharya, D.K.: Development of a simple, blood based lymphoproliferation assay to assess the clinical status of patients with acute lymphoblastic leukemia. Leuk. Res. 23, 433–439 (1999). 10.1016/S0145-2126(98)00184-2

    Article  PubMed  CAS  Google Scholar 

  15. Sinha, D., Bhattacharya, D.K., Mandal, C.: A colorimetric assay to evaluate the chemotherapeutic response of children with acute lymphoblastic leukemia (ALL) employing achatininH: a 9-O-acetyl sialic acid binding lectin. Leuk. Res. 23, 803–809 (1999). 10.1016/S0145-2126(99)00093-4

    Article  PubMed  CAS  Google Scholar 

  16. Pal, S., Ghosh, S., Bandyopadhyay, S., Mandal, C., Bandyopadhyay, S., Bhattacharya, D.K., et al.: 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 (2004). doi:10.1002/ijc.20246

    Article  PubMed  CAS  Google Scholar 

  17. Pal, S., Ghosh, S., Mandal, C., Kohla, G., Brossmer, R., Isecke, R., et al.: Purification and characterization of 9-O-acetylated sialoglycoproteins from leukemic cells and their potential as immunological tool for monitoring childhood acute lymphoblastic leukemia. Glycobiology 14, 859–870 (2004). doi:10.1093/glycob/cwh111

    Article  PubMed  CAS  Google Scholar 

  18. Chowdhury, S., Bandyopadhyay, S., Chandra, S., Mandal, C.: 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 (2007)

    PubMed  CAS  Google Scholar 

  19. Chowdhury, S., Bandyopadhyay, S., Mandal, C., Chandra, S., Mandal, C.: 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 (2008). doi:10.1186/1471-2407-8-40

    Article  PubMed  PubMed Central  Google Scholar 

  20. Storms, R.W., Green, P.D., Safford, K.M., Niedzwiecki, D., Cogle, C.R., Colvin, O.M., et al.: Distinct hematopoietic progenitor compartments are delineated by the expression of aldehyde dehydrogenase and CD34. Blood 106, 95–102 (2005). doi:10.1182/blood-2004-09-3652

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  21. Jones, R.J., Barber, J.P., Vala, M.S., Collector, M.I., Kaufmann, S.H., Ludeman, S.M., et al.: Assessment of aldehyde dehydrogenase in viable cells. Blood 85, 2742–2746 (1995)

    PubMed  CAS  Google Scholar 

  22. Kastan, M.B., Schlaffer, E., Russo, J.E., Colvin, O.M., Civin, C.I., Hilton, J.: Direct demonstration of elevated aldehyde dehydrogenase in human hematopoietic progenitor cells. Blood 75, 1947–1950 (1990)

    PubMed  CAS  Google Scholar 

  23. Storms, R.W., Trujillo, A.P., Springer, J.B., Shah, L., Colvin, O.M., Ludeman, S.M., et al.: Isolation of primitive human hematopoietic progenitors on the basis of aldehyde dehydrogenase activity. Proc. Natl. Acad. Sci. U. S. A. 96, 9118–9123 (1999). doi:10.1073/pnas.96.16.9118

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  24. Hess, D.A., Meyerrose, T.E., Wirthlin, L., Craft, T.P., Herrbrich, P.E., Creer, M.H., et al.: Functional characterization of highly purified human hematopoietic repopulating cells isolated according to aldehyde dehydrogenase activity. Blood 104, 1648–1655 (2004). doi:10.1182/blood-2004-02-0448

    Article  PubMed  CAS  Google Scholar 

  25. Pearce, D.J., Taussig, D., Simpson, C., Allen, K., Rohatiner, A.Z., Lister, T.A., et al.: Characterization of cells with a high aldehyde dehydrogenase activity from cord blood and acute myeloid leukemia samples. Stem Cells 23, 752–760 (2005). doi:10.1634/stemcells.2004-0292

    Article  PubMed  CAS  Google Scholar 

  26. Jennings, C.D., Foon, K.A.: Recent advances in flow cytometry: application to the diagnosis of hematologic malignancy. Blood 90, 2863–2892 (1997)

    PubMed  CAS  Google Scholar 

  27. Lacombe, F., Durrieu, F., Briais, A., Dumain, P., Belloc, F., Bascans, E., et al.: Flow cytometry CD45 gating for immunophenotyping of acute myeloid leukemia. Leukemia 11, 1878–1886 (1997)

    Article  PubMed  CAS  Google Scholar 

  28. Behm, F.G., Raimondi, S.C., Schell, M.J., Look, A.T., Rivera, G.K., Pui, C.H.: Lack of CD45 antigen on blast cells in childhood acute lymphoblastic leukemia is associated with chromosomal hyperdiploidy and other favorable prognostic features. Blood 79, 1011–1016 (1992)

    PubMed  CAS  Google Scholar 

  29. Pal, S., Chatterjee, M., Bhattacharya, D.K., Bandhyopadhyay, S., Mandal, C., Mandal, C.: O-Acetyl sialic acid specific IgM in childhood acute lymphoblastic leukemia. Glycoconjugate J. 18, 529–537 (2001)

    Article  CAS  Google Scholar 

  30. Chowdhury, S., Mandal, C., Sarkar, S., Bag, A.K., Vlasak, R., Chandra, S., Mandal, C.: Mobilization of lymphoblasts from bone marrow to peripheral blood in childhood acute lymphoblastic leukaemia: role of 9-O-acetylated sialoglycoproteins. Leuk. Res. 36, 146–155 (2012). 10.1016/j.leukres.2011.10.017

    Article  PubMed  CAS  Google Scholar 

  31. Goodell, M.A., Rosenzweig, M., Kim, H., Marks, D.F., DeMaria, M., Paradis, G., et al.: Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species. Nat. Med. 3, 1337–1345 (1997)

    Article  PubMed  CAS  Google Scholar 

  32. Bhatia, M., Bonnet, D., Murdoch, B., Gan, O.I., Dick, J.E.: A newly discovered class of human hematopoietic cells with SCID-repopulating activity. Nat. Med. 4, 1038–1045 (1998). 10.1038/2023

    Article  PubMed  CAS  Google Scholar 

  33. Jones, R.J., Collector, M.I., Barber, J.P., Vala, M.S., Fackler, M.J., May, W.S., et al.: Characterization of mouse lymphohematopoietic stem cells lacking spleen colony-forming activity. Blood 88, 487–491 (1996)

    PubMed  CAS  Google Scholar 

  34. Li, C.L., Johnson, G.R.: Rhodamine123 reveals heterogeneity within murine Lin-, Sca-1+ hemopoietic stem cells. J. Exp. Med. 175, 1443–1447 (1992)

    Article  PubMed  CAS  Google Scholar 

  35. Spangrude, G.J., Brooks, D.M., Tumas, D.B.: Long-term repopulation of irradiated mice with limiting numbers of purified hematopoietic stem cells: in vivo expansion of stem cell phenotype but not function. Blood 85, 1006–1016 (1995)

    PubMed  CAS  Google Scholar 

  36. Yonemura, Y., Ku, H., Hirayama, F., Souza, L.M., Ogawa, M.: Interleukin 3 or interleukin 1 abrogates the reconstituting ability of hematopoietic stem cells. Proc. Natl. Acad. Sci. U. S. A. 93, 4040–4044 (1996)

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  37. Randall, T.D., Weissman, I.L.: Characterization of a population of cells in the bone marrow that phenotypically mimics hematopoietic stem cells: resting stem cells or mystery population? Stem Cells 16, 38–48 (1998). doi:10.1002/stem.160038

    Article  PubMed  CAS  Google Scholar 

  38. Jordan, C.T.: The leukemic stem cell. Best Pract. Res. Clin. Haematol. 20, 13–18 (2007). 10.1016/j.beha.2006.10.005

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  39. Ghosh, S., Bandyopadhyay, S., Mallick, A., Pal, S., Vlasak, R., Bhattacharya, D.K., et al.: Interferon gamma promotes survival of lymphoblasts over expressing 9-O-acetylated sialoglycoconjugates in childhood acute lymphoblastic leukaemia (ALL). J. Cell. Biochem. 95, 206–216 (2005). doi:10.1002/jcb.20382

    Article  PubMed  CAS  Google Scholar 

  40. Ghosh, S., Bandyopadhyay, S., Pal, S., Das, B., Bhattacharya, D.K., Mandal, C.: 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 (2005). doi:10.1111/j.1365-2141.2004.05256.x

    Article  PubMed  CAS  Google Scholar 

  41. Mukherjee, K., Chowdhury, S., Mondal, S., Mandal, C., Chandra, S., Bhadra, R.K., et al.: 9-O-acetylated GD3 triggers programmed cell death in mature erythrocytes. Biochem. Biophys. Res. Commun. 362, 651–657 (2007). 10.1016/j.bbrc.2007.08.048

    Article  PubMed  CAS  Google Scholar 

  42. Mandal, C., Srinivasan, G.V., Chowdhury, S., Chandra, S., Mandal, C., Schauer, R., et al.: High level of sialate-O-acetyltransferase activity in lymphoblasts of childhood acute lymphoblastic leukaemia (ALL): enzyme characterization and correlation with disease status. Glycoconjugate J. 26, 57–73 (2008)

    Article  Google Scholar 

  43. Srinivasan, G.V., Schauer, R. Assays of sialate-O-acetyltransferases and sialate-O-acetylesterases. Glycoconjugate J. 2008

  44. Mandal, C., Tringali, C., Mondal, S., Anastasia, L., Chandra, S., Venerando, B., Mandal, C.: 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, 337–349 (2010). doi:10.1002/ijc.24733

    Article  PubMed  CAS  Google Scholar 

  45. Mandal, C., Mandal, C., Chandra, S., Schauer, R., Mandal, C.: Regulation of O-acetylation of sialic acids by sialate-O-acetyltransferase and sialate-O-acetylesterase activities in childhood acute lymphoblastic leukemia. Glycobiology 22, 70–83 (2012). doi:10.1093/glycob/cwr106

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We sincerely acknowledge CSIR-IICB, CSIR (IAP-0001, HCP004, NMITLI, TLP-004) and DBT (GAP 235), Department of Science and Technology (DST), ICMR Govt. of India New Delhi. CM is grateful to financial support by J.C. Bose Fellowship, DST and mutual grant from ICMR and German Cancer Research Centre. The authors thank Mr. Asish Mullick for his excellent technical assistance. Mr. Chandan Mandal, Mr. Kaushik Bhattacharya and Ms Susmita Mondal are sincerely acknowledged for their help in carrying out some of the experiments.

Author information

Authors and Affiliations

  1. Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata, 700 032, India

    Suchandra Chowdhury & Chitra Mandal

  2. Clinical Haematology Service, 4, Gorky Terrace, Kolkata, 700 017, India

    Sarmila Chandra

Authors
  1. Suchandra Chowdhury
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sarmila Chandra
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chitra Mandal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chitra Mandal.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chowdhury, S., Chandra, S. & Mandal, C. 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, 523–535 (2014). https://doi.org/10.1007/s10719-014-9550-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10719-014-9550-x

Keywords

Search

Navigation