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Protein Kinase C Blockade Inhibits Differentiation of Myeloid Blasts into Dendritic Cells by Calcium Ionophore A23187

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Abstract

Direct differentiation of myeloid leukemia blasts into antigen-presenting dendritic cells (DCs) for use as cellular vaccines is unique in that identification of tumor-specific antigens may not be necessary because the antigens should already be endogenously expressed.We hypothesized that signaling through protein kinase C (PKC) is required for differentiation of HL-60 promyeloblasts into DCs upon stimulation with calcium ionophore A23187. To demonstrate the inhibitory effect of PKC blockade, we pretreated HL-60 myeloid blasts with the protein kinase inhibitor bisindolylmaleimide I (Bis-1) for 24 hours and then treated the cells with calcium ionophore A23187 for an additional 24 hours. Controls consisted of HL-60 blasts treated with A23187, Bis-1 alone, or media.We noted that blasts cultured in media, Bis-1, or Bis-1 then A23187 did not develop the morphologic and phenotypic DC characteristics, up-regulate Rel B, or activate allogeneic T-cells. Our findings suggested that PKC blockade inhibits morphologic, phenotypic, and functional differentiation of HL-60 promyeloblasts into antigen-presenting DCs. Our findings supported the role of PKC as an obligatory pathway for calcium ionophore A23187-induced differentiation of HL-60 myeloblasts into antigen-presenting DCs.

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Authors and Affiliations

  1. Section of Hematology-Oncology, University of Oklahoma Health Sciences Center and OU Cancer Center, Oklahoma City

    Qian Li & Howard Ozer

  2. Department of Medicine, University of Oklahoma Health Sciences Center, 920 Stanton L.Young Blvd, WP 2080, 73104, Oklahoma City, OK, USA

    Howard Ozer & Mohamed A. Kharfan-Dabajaa

  3. Division of Hematology-Oncology and Department of Microbiology and Immunology, University of Miami, Miami, Florida, USA

    Inna Lindner & Kelvin P. Lee

Authors
  1. Qian Li
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  2. Howard Ozer
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  3. Inna Lindner
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  4. Kelvin P. Lee
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  5. Mohamed A. Kharfan-Dabajaa
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Corresponding author

Correspondence to Mohamed A. Kharfan-Dabajaa.

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Li, Q., Ozer, H., Lindner, I. et al. Protein Kinase C Blockade Inhibits Differentiation of Myeloid Blasts into Dendritic Cells by Calcium Ionophore A23187. Int J Hematol 81, 131–137 (2005). https://doi.org/10.1532/IJH97.NA0405

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  • DOI: https://doi.org/10.1532/IJH97.NA0405

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