Dendritic cells generated from acute myeloid leukemia (AML) blasts maintain the expression of immunogenic leukemia associated antigens

Cancer Immunol Immunother. 2005 Jul;54(7):685-93. doi: 10.1007/s00262-004-0631-8. Epub 2004 Dec 31.


Recently, the focus is on new specific immunotherapies for AML such as cellular therapies employing dendritic cells (DCs) generated from AML blasts. AML-DCs express constitutionally leukemia-associated antigens (LAAs) present in AML blasts they are generated from. Here we investigated whether the generation of AML-DCs would alter the expression level of LAAs. Moreover, we evaluated the presence of HLA and costimulatory molecules on AML blasts versus AML-DCs. Quantitative real-time polymerase chain reaction (PCR) was performed for the following LAAs: preferentially expressed antigen in melanoma (PRAME), the receptor for hyaluronic acid mediated motility (RHAMM/CD168), Wilms' tumor gene 1 (WT-1) and proteinase 3. The expression of HLA-ABC, HLA-DR, CD40, CD80, CD83 and CD86 was evaluated by flow cytometry. RHAMM protein expression was evaluated by immunocytochemistry, recognition of AML-DCs by PRAME epitope-specific T cells was evaluated in a chromium-release assay. Quantitative real-time PCR for AML-DCs versus AML blasts showed an alteration in mRNA expression of LAAs. An elevated PCR signal for PRAME was detected in 7/12 AML-DC preparations. 6/12 AML-DC preparations showed a significant upregulation of the PCR signal for RHAMM. A stronger WT-1 and proteinase-3 signal was observed in PCR for only 2/12 and 1/12 AML-DCs , respectively. All preparations showed a strong expression of at least one of the LAAs examined. As demonstrated by flow cytometry, AML-DCs strongly upregulated costimulatory molecules like CD40 and CD80 in comparison with AML blasts. AML-DCs tested positive for RHAMM protein. PRAME positive AML-DCs were recognized by specific T cells. AML-DCs might constitute a powerful tool in immunotherapy for AML. Real-time PCR allows a quick and quantitative assessment of immunologically relevant LAA expression with only 10(5) DCs and might be helpful for the decision whether the AML-DC vaccination strategy is favourable or not.

MeSH terms

  • Acute Disease
  • Antigens, CD / metabolism
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / metabolism
  • Blast Crisis
  • Cell Survival / immunology
  • Dendritic Cells / immunology*
  • Extracellular Matrix Proteins / metabolism
  • HLA-DR Antigens / metabolism
  • Humans
  • Hyaluronan Receptors / metabolism
  • Leukemia, Myeloid / immunology*
  • Leukemia, Myeloid / pathology
  • Myeloblastin
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serine Endopeptidases / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Tumor Cells, Cultured
  • WT1 Proteins / metabolism


  • Antigens, CD
  • Antigens, Neoplasm
  • Extracellular Matrix Proteins
  • HLA-DR Antigens
  • Hyaluronan Receptors
  • PRAME protein, human
  • RNA, Neoplasm
  • WT1 Proteins
  • hyaluronan-mediated motility receptor
  • Serine Endopeptidases
  • Myeloblastin