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Peptides spanning the fusion region of Abl/Bcr are immunogenic and sensitize CD8+ T lymphocytes to recognize native chronic myelogenous leukemia

Leukemia volume 16, pages 2341–2343 (2002)Cite this article

Chronic myelogenous leukemia is characterized by a reciprocal translocation, t(9;22)(q34;q11), between the long arms of chromosomes 9 and 22, leading to the Philadelphia chromosome. Two fusion genes are created by this translocation: bcr/abl and abl/bcr. The fusion regions of both translocation products are unique and strictly limited to leukemia cells, giving rise to potential tumor-specific antigens.

Current treatment options for CML include stem cell transplantation, and hydroxyurea-based or interferon-α-based regimens.1 Much attention has been focused recently on the newly introduced tyrosine kinase inhibitor STI571 with its striking effect in almost all patients. However, resistance to STI571 as a single agent occurs frequently and rapidly, and allogeneic stem cell transplantation is still regarded as the only curative treatment for CML. The latter is thought to depend on a T cell-mediated graft-versus-leukemia effect (GVL) distinct from the graft-versus-host effect, suggesting specific recognition of tumor cells by the immune system. This effect may also be achieved by administration of donor leukocyte infusions after relapse in transplant recipients. Although GVL is largely caused by differences in major and minor histocompatibility antigens between donor and recipient, there is also evidence for leukemia-specific recognition. Vaccination with tumor-specific antigens could enhance or initiate antileukemic effects.2

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Acknowledgements

We would like to thank Dr Medi Adibzadeh, Tübingen, for helping to initiate these studies, Prof W Voelter and Dr Hubert Kalbacher for peptide synthesis and Dr Martin Deeg for assistance with mass spectrometry. We thank Prof Jesper Zeuthen for providing class-I peptides and Prof CA Müller for HLA typing. We thank the patients who provided blood samples and their physicians for making them available for this study. This work was supported by the Mildred Scheel Foundation for Cancer Research (Deutsche Krebshilfe) Grant No. 10-1173-Pa3 and the Dieter Schlag Foundation for Research into Diseases of the Blood. The peptide sensitization protocols were developed as part of an EU collaborative project (EUCAPS, contract BMH4-CT98-3058, coordinated by G Pawelec).

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  1. Second Department of Internal Medicine, Section for Transplantation Immunology and Immunohaematology, Tübingen University Medical School, Tübingen, Germany

    WM Wagner, Q Ouyang & G Pawelec

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  1. WM Wagner
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  2. Q Ouyang
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Wagner, W., Ouyang, Q. & Pawelec, G. Peptides spanning the fusion region of Abl/Bcr are immunogenic and sensitize CD8+ T lymphocytes to recognize native chronic myelogenous leukemia. Leukemia 16, 2341–2343 (2002). https://doi.org/10.1038/sj.leu.2402687

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