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Induction of folate receptor type β in a bone marrow engraftment model of acute myelogenous leukemia

Leukemia volume 21, pages 2233–2235 (2007)Cite this article

The glycosyl-phosphatidylinositol-anchored folate receptor (FR) has been widely recognized as a potential target for the selective delivery of therapeutic agents to pathological tissues.1 This is because of the narrow tissue specificity of FR expression in normal tissues, its restricted expression at the luminal surface of epithelial cells that is inaccessible to the circulation, the ability of the receptor to bind and internalize both small and particulate chemical conjugates of folic acid and the ability of the receptor to mediate various types of immunotherapy. The α subtype of FR has served as a therapeutic target in many promising pre-clinical and clinical studies of carcinomas, whereas FRβ expressed in activated macrophage has proven to be a promising target in the treatment of inflammatory diseases.2

We have previously reported that the expression of FRβ is limited to the myelomonocytic lineage and that its expression is increased during neutrophil maturation and during the activation of macrophage;3, 4 however, among normal hematopoietic cells, only the receptor expressed in activated macrophage is functional in having the ability to bind folate.4, 5 FRβ is also expressed in a functional form in approximately 70% of acute myelogenous leukemia (AML) in which it is frequently coexpressed with CD34.6 These observations suggest that FRβ is a potential target for drug delivery to AML cells, but prospects of its clinical utility are limited by the variable and the frequently low expression of the receptor in the leukemic cells of AML patients.6

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References

  1. Elnakat H, Ratnam M . Distribution, functionality and gene regulation of folate receptor isoforms: implications in targeted therapy. In: Low PS, Anthony AC (eds). Advanced Drug Delivery Reviews, vol. 56. Elsevier: Amsterdam, The Netherlands, 2004, pp 1067–1084.

    Google Scholar 

  2. Paulos CM, ZTurk MJ, Breur GJ, Low PS . Folate receptor-mediated targeting of therapeutic and imaging agents to activated macrophages in rheumatoid arthritis. In: Low PS, Anthony AC (eds). Advanced Drug Delivery Reviews, vol. 56. Elsevier: Amsterdam, The Netherlands, 2004, pp 1205–1218.

    Google Scholar 

  3. Ross JF, Wang H, Mathew P, Wu M, Booth R, Ratnam M . Folate receptor type β is a neutrophilic lineage marker and is differentially expressed in myeloid leukemia. Cancer 1999; 85: 348–357.

    Article  CAS  PubMed  Google Scholar 

  4. Nakashima-Matsushita N, Homma T, Yu S, Matsuda T, Sunahara N, Nakemura T et al. Selective expression of folate receptor beta and its possible role in methotrexate transport in synovial macrophages from rheumatoid arthritis patients. Arthritis Rheum 1999; 42: 1609–1616.

    Article  CAS  PubMed  Google Scholar 

  5. Pan XQ, Zheng X, Shi G, Wang H, Ratnam M, Lee RJ . Strategy for the treatment of acute myelogenous leukemia based on folate receptor β-targeted liposomal doxorubicin combined with receptor induction using all-trans retinoic acid. Blood 2002; 100: 594–602.

    Article  CAS  PubMed  Google Scholar 

  6. Wang H, Zheng X, Behm FG, Ratnam M . Differentiation-independent retinoid induction of folate receptor type β, a potential tumor target in myeloid leukemia. Blood 2000; 96: 3529–3536.

    CAS  PubMed  Google Scholar 

  7. Hao H, Qi H, Ratnam M . Modulation of folate receptor type β gene by coordinate interactions of retinoic acid receptors at activator Sp1 and repressor AP1 sites. Blood 2003; 101: 4551–4560.

    Article  CAS  PubMed  Google Scholar 

  8. Qi H, Ratnam M . Synergistic induction of folate receptor β by all-trans retinoic acid and histone deacetylase inhibitors in acute myelogenous leukemia cells: mechanism and utility in enhancing selective antifolate cytotoxicity. Cancer Res 2006; 66: 5875–5882.

    Article  CAS  PubMed  Google Scholar 

  9. Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Canceres-Cortes J et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 1994; 367: 645–648.

    Article  CAS  PubMed  Google Scholar 

  10. Sutherland HJ, Blair A, Zapf RW . Characterization of a hierarchy in human acute myeloid leukemia progenitor cells. Blood 1996; 87: 4754–4761.

    CAS  PubMed  Google Scholar 

  11. Bonnet D, Dick JE . Human acute myeloid leukemia is organized as a hierarchy originates from a primitive hematopoietic cell. Nat Med 1997; 3: 730–737.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by NIH RO1 Grant CA080183 to MR and Grant CA095673 to RJL. MR also received support from a Harold and Helen McMaster endowment.

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  1. B W Blaser and M Gonit: These authors contributed equally to this work

Authors and Affiliations

  1. Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA

    B W Blaser, M Guimond & R J Lee

  2. Department of Biochemistry and Cancer Biology, Medical University of Ohio, Toledo, OH, USA

    M Gonit, H Qi, A Shatnawi & M Ratnam

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  1. B W Blaser
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  2. M Gonit
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  7. M Ratnam
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Correspondence to M Ratnam.

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Blaser, B., Gonit, M., Qi, H. et al. Induction of folate receptor type β in a bone marrow engraftment model of acute myelogenous leukemia. Leukemia 21, 2233–2235 (2007). https://doi.org/10.1038/sj.leu.2404786

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