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Acute Leukemias

In situ analysis of the antigen-processing machinery in acute myeloid leukaemic blasts by tissue microarray

Leukemia volume 23, pages 877–885 (2009)Cite this article

Abstract

Altered expression of major histocompatibility complex (MHC) class I molecules can be caused by defects in genes of the antigen-processing machinery (APM), and is often correlated to progression in solid tumours. However, little is known about expression of the APM components in blasts from patients with acute myeloid leukaemia (AML). In this study, we investigated the expression of the APM components large multifunctional peptidases (LMP) 2 and 7, transporter-associated with antigen processing (TAP) 1 and 2, β-2-microglobulin (β2m) and MHC class I heavy chain in situ by tissue microarray from bone marrow biopsies of 30 AML patients. APM components were heterogeneously expressed in all AML samples tested, but no significant correlation with the AML subtype according to the French-American-British classification was found. Depending on the APM component tested, up to 90% of the trephines showed no or weak expression, whereas the LMP7 protein was detected in 66% of all samples. By following disease progression in individual AML patients, we found severe downregulation of APM components in two out of four patients from initial diagnosis to relapse. We conclude that downregulation of APM components may play a role in the failure of immuno-surveillance and may therefore contribute to relapse in acute leukaemia.

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Acknowledgements

We thank Dr Soldano Ferrone for providing the mAbs against the antigen-processing machinery. This study was supported by the German José Carreras Leukemia Foundation (DJCS R 06/15v).

Author information

Author notes

  1. S Hoves and M Aigner: These authors contributed equally to this work.

  2. E C Obermann and A Mackensen: These authors contributed equally to this work and should be considered joint senior author.

Authors and Affiliations

  1. Department of Haematology and Oncology, University of Regensburg, Regensburg, Germany

    S Hoves, M Aigner, M Laumer & A Mackensen

  2. Department of Internal Medicine 5—Haematology and Oncology, University of Erlangen-Nürnberg, Erlangen, Germany

    M Aigner & A Mackensen

  3. Institute of Pathology, University of Regensburg, Regensburg, Germany

    C Pfeiffer & E C Obermann

  4. Institute of Pathology, University of Basel, Basel, Switzerland

    E C Obermann

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  1. S Hoves
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  2. M Aigner
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  4. M Laumer
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Corresponding author

Correspondence to A Mackensen.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Hoves, S., Aigner, M., Pfeiffer, C. et al. In situ analysis of the antigen-processing machinery in acute myeloid leukaemic blasts by tissue microarray. Leukemia 23, 877–885 (2009). https://doi.org/10.1038/leu.2008.391

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