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Interferon-α induces dendritic cell differentiation of CML mononuclear cells in vitro and in vivo

Leukemia volume 16, pages 1484–1489 (2002)Cite this article

Abstract

The ability of interferon-α (IFN-α) to induce dendritic cell (DC) differentiation in chronic myeloid leukemia (CML) was evaluated. Peripheral blood mononuclear cells from CML patients cultured with IFN-α and granulocyte–macrophage colony-stimulating factor (GM-CSF) developed a dendritic morphology. Fluorescence in situ hybridization demonstrated that the DCs harbored the bcr/abl translocation. The DCs prepared with IFN-α/GM-CSF expressed significantly higher levels of class I and II HLA than those grown in interleukin-4 (IL-4) and GM-CSF. The DCs prepared from newly diagnosed CML patients using IFN-α/GM-CSF expressed immunoregulatory proteins at levels comparable to normal DCs. In contrast, DCs cultured from CML patients who did not achieve a cytogenetic response to IFN-α expressed significantly lower levels of class I HLA, CD40, CD54, CD80 and CD86 than normal DCs. The expression of CD86 by CML DCs was enhanced when they were cultured with IFN-α/IL-4/GM-CSF, or when IFN-α/GM-CSF-treated cells were induced to mature by CD40 ligand. The DCs from IFN-α failures were less stimulatory than normal DCs in the allogeneic mixed leukocyte reaction. CML patients who had a cytogenetic response to IFN-α initially had low numbers of bone marrow DCs that increased significantly with treatment, while nonresponders had more prevalent DCs at baseline that showed no consistent change with treatment. Therefore, IFN-α can induce DC differentiation from CML progenitor cells both in vitro and in vivo. The therapeutic activity of IFN-α in CML may be due to its ability to stimulate the generation of DCs that can present CML-specific antigens. Resistance to IFN-α may result when DC differentiation becomes impaired.

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Acknowledgements

This research was supported by grants from the Leukemia and Lymphoma Society of America, the UCLA Jonsson Cancer Center Foundation and the University of California Cancer Research Coordinating Committee. Additional support came from the Perry Cohan Fund.

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Authors and Affiliations

  1. UCLA Department of Medicine, Division of Hematology/Oncology, Los Angeles, CA, USA

    RL Paquette, N Hsu, G Shih, G Schiller, C Sawyers & JA Glaspy

  2. UCLA Department of Pathology, Los Angeles, CA, USA

    J Said, M Mohammed & NP Rao

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  1. RL Paquette
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  2. N Hsu
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Paquette, R., Hsu, N., Said, J. et al. Interferon-α induces dendritic cell differentiation of CML mononuclear cells in vitro and in vivo. Leukemia 16, 1484–1489 (2002). https://doi.org/10.1038/sj.leu.2402602

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