Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Molecular Targets for Therapy

Molecular recognition of acute myeloid leukemia using aptamers

Leukemia volume 23, pages 235–244 (2009)Cite this article

Abstract

Cell surface proteins can play important roles in cancer pathogenesis. Comprehensive understanding of the surface protein expression patterns of tumor cells and, consequently, the pathogenesis of tumor cells depends on molecular probes against these proteins. To be used effectively for tumor diagnosis, classification and therapy, such probes would be capable of specific binding to targeted tumor cells. Molecular aptamers, designer DNA–RNA probes, can address this challenge by recognizing proteins, peptides and other small molecules with high affinity and specificity. Through a process known as cell-based SELEX, we used live acute myeloid leukemia (AML) cells to select a group of DNA aptamers, which can recognize AML cells with dissociation constants (Kd's) in the nanomolar range. Interestingly, one aptamer (KH1C12) compared with two control cell lines (K562 and NB4) showed significant selectivity to the target AML cell line (HL60) and could recognize the target cells within a complex mixture of normal bone marrow aspirates. The other two aptamers KK1B10 and KK1D04 recognize targets associated with monocytic differentiation. Our studies show that the selected aptamers can be used as a molecular tool for further understanding surface protein expression patterns on tumor cells and thus providing a foundation for effective molecular analysis of leukemia and its subcategories.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  1. Ikeda A, Shankar DB, Watanabe M, Tamanoi F, Moore TB, Sakamoto KM . Molecular targets and the treatment of myeloid leukemia. Mol Genet Metab 2006; 88: 216–224.

    Article  CAS  PubMed  Google Scholar 

  2. Aribi A, Ravandi F, Giles F . Novel agents in acute myeloid leukemia. Cancer J 2006; 12: 77–91.

    CAS  PubMed  Google Scholar 

  3. Shangguan D, Li Y, Tang Z, Cao Z, Cao ZC, Chen HW et al. Aptamers evolved from live cells as effective molecular probes for cancer study. Proc Natl Acad Sci USA 2006; 103: 11838–11843.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Tang Z, Shangguan D, Wang K, Shi H, Sefah K, Mallikratchy P et al. Selection of aptamers for molecular recognition and characterization of cancer cells. Anal Chem 2007; 79: 4900–4907.

    Article  CAS  PubMed  Google Scholar 

  5. Labbaye C, Zhang J, Casanova J-L, Lanotte M . Regulation of myeloblastin messenger RNA expression in myeloid leukemia cells treated with all-trans retinoic acid. Blood 1993; 81: 475–481.

    CAS  PubMed  Google Scholar 

  6. Bhatia M, Kirkland JB, Meckling-Gill KA . Monocytic Differentiation of Promyelocytic Leukemia Cells in Response to 1,25-Dihydroxyvitamin D3 Is Independent of Nuclear Receptor Binding. J. Biol. Chem 1995; 270: 15962–15965.

    Article  CAS  PubMed  Google Scholar 

  7. Leupin N, Kuhn A, Hügli B, Grob TJ, Jaggi R, Tobler A et al. Gene expression profiling reveals consistent differences between clinical samples of human leukemia and their model cell lines. Br J Hematol 2006; 135: 520–523.

    Article  CAS  Google Scholar 

  8. Olins AL, Hermann H, Lichter P, Olins DE . Retinoic acid differentiation of HL-60 cells promotes cytoskeletal polarization. Exp Cell Res 2000; 254: 130–142.

    Article  CAS  PubMed  Google Scholar 

  9. Marques-Silva VM, De Souza MHO, Teixeira MCL, Arcuri RA, Rumjanek VM . Myeloid leukemia differentiation by phorbol ester and retinoic acid: a practical approach. J Clin Lab Anal 1990; 4: 342–349.

    Article  CAS  PubMed  Google Scholar 

  10. Mollinedo F, Gajate C, Tugores A, Flores I, Naranjo JR . Differences in expression of transcription factor AP-1 in human promyelocytic HL60 cells during differentiation towards macrophages versus granulocytes. Biochem J 1993; 294: 137–144.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Boyd AW, Metcalf D . Induction of differentiation in HL60 leukemia cells: a cell cycle dependent all-or-none event. Leuk Res 1984; 8: 27–43.

    Article  CAS  PubMed  Google Scholar 

  12. Collins JS . The HL60 promyelocytic leukemia cell line: proliferation, differentiation, and cellular oncogene expression. Blood 1987; 70: 1233–1244.

    CAS  PubMed  Google Scholar 

  13. Griffin DJ, Larcom P, Schlossman FS . Use of surface markers to identify a subset of acute myelomonocytic leukemia cells with progenitor cell properties. Blood 1983; 62: 1300–1303.

    CAS  PubMed  Google Scholar 

  14. Cerchia L, Ducongé F, Pestourie C, Boulay J, Aissouni Y, Gombert K et al. Neutralizing aptamers from whole-cell SELEX inhibit the RET receptor tyrosine kinase. PLoS Biol 2005; 3: 0697–0704.

    Article  CAS  Google Scholar 

  15. Zheng X, Ravatn R, Lin Y, Shih W-C, Rabson A, Strair EH et al. Gene expression of TPA induced differentiation in HL60 cells by DNA microarray analysis. Nucleic Acids Res 2002; 30: 4489–4499.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Yang L, Zhao H, Li SW, Ahrens K, Collins C, Eckenrode S et al. Gene expression profiling during all-trans retinoic acid-induced cell differentiation of acute promyelocytic leukemia cells. J Mol Diagn 2003; 5: 212–221.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Chomienne C, Ballerini P, Balitrand N, Daniel MT, Fenaux P, Castaigne S et al. All-trans retinoic acid in acute promyelocytic leukemias. II. In vitro studies: structure-function relationship. Blood 1990; 76: 1710–1717.

    CAS  PubMed  Google Scholar 

  18. Collins SJ, Robertson KA, Mueller L . Retinioc acid-induced granulocytic differentiation of HL60 myeloid leukemia is mediated directly through the retinoic acid receptor (RAR-α). Mol Cell Biol 1990; 10: 2154–2163.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Shangguan D, Cao Z, Meng L, Mallikaratchy P, Sefah K, Wang H et al. Cell-specific aptamer probes for membrane protein elucidation in cancer cells. Journal of Proteome Research 2008; 7: 2133–2139.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Mallikaratchy P, Tang Z, Meng L, Shangguan D, Sefah K, Tan W . Aptamer directly evolved from live cells recognizes membrane bound immunoglobin heavy mu chain in Burkitt's Lymphoma cells. Molecular and Cellular Proteomics 2007; 6: 2230–2238.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the DNA sequencing core, ICBR at the University of Florida. This work is supported by NIH GM079359 and CA122648, and NSF grant.

Author information

Authors and Affiliations

  1. Department of Chemistry, Center for Research at Bio/nano Interface, University of Florida, Gainesville, FL, USA

    K Sefah, Z W Tang, D H Shangguan, H Chen, D Lopez-Colon, P Parekh, J Martin, L Meng, J A Phillips, Y M Kim & W H Tan

  2. Shands Cancer Center, University of Florida, Gainesville, FL, USA

    K Sefah, Z W Tang, D H Shangguan, H Chen, D Lopez-Colon, P Parekh, J Martin, L Meng, J A Phillips, Y M Kim & W H Tan

  3. Department of Pathology, University of Florida, Gainesville, FL, USA

    Y Li

  4. Department of Physiology and Functional Genomics, UF Genetics Institute and McKnight Brain Institute, University of Florida, Gainesville, FL, USA

    W H Tan

  5. Moffit Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL, USA

    W H Tan

Authors
  1. K Sefah
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Z W Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D H Shangguan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D Lopez-Colon
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Y Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. P Parekh
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. L Meng
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. J A Phillips
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Y M Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. W H Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to W H Tan.

Additional information

Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sefah, K., Tang, Z., Shangguan, D. et al. Molecular recognition of acute myeloid leukemia using aptamers. Leukemia 23, 235–244 (2009). https://doi.org/10.1038/leu.2008.335

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2008.335

Keywords

This article is cited by

Search

Advanced search

Quick links