The immunogenicity of Bcr-Abl expressing dendritic cells is dependent on the Bcr-Abl kinase activity and dominated by Bcr-Abl regulated antigens

Blood. 2007 Oct 1;110(7):2556-60. doi: 10.1182/blood-2007-01-071001. Epub 2007 Jun 19.


In Ph(+) chronic myeloid leukemia (CML), the constitutively active Bcr-Abl kinase leads to the up-regulation and activation of multiple genes, which may subsequently result in the expression of leukemia-associated antigens. In this study, we investigated the immunogenicity of Bcr-Abl-regulated antigens by stimulating CD8(+) T lymphocytes with autologous dendritic cells transfected with RNA coding for Bcr-Abl wild-type or a kinase-deficient mutant. Significant HLA class I-restricted T-cell responses were detected against antigens regulated by the Bcr-Abl kinase, but not toward the Bcr-Abl protein itself. The T-cell repertoire of a patient with CML in major molecular remission due to imatinib mesylate was also dominated by T cells directed against Bcr-Abl-regulated antigens. These results encourage the development of immunotherapeutic approaches against Bcr-Abl-regulated antigens for the treatment of CML patients with residual disease following therapy with Bcr-Abl kinase inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / immunology*
  • Benzamides
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Enzyme Activation / drug effects
  • Fusion Proteins, bcr-abl / antagonists & inhibitors
  • Fusion Proteins, bcr-abl / genetics
  • Fusion Proteins, bcr-abl / immunology*
  • Fusion Proteins, bcr-abl / metabolism*
  • Gene Expression Regulation, Neoplastic*
  • HLA Antigens / metabolism
  • Humans
  • Imatinib Mesylate
  • Immunogenetics*
  • Leukemia / immunology
  • Leukemia / metabolism
  • Lymphocyte Activation / immunology
  • Piperazines / pharmacology
  • Pyrimidines / pharmacology
  • Up-Regulation
  • Xenopus laevis


  • Antigens
  • Benzamides
  • HLA Antigens
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl