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High expression of activation-induced cytidine deaminase (AID) mRNA is associated with unmutated IGVH gene status and unfavourable cytogenetic aberrations in patients with chronic lymphocytic leukaemia

Leukemia volume 18, pages 756–762 (2004)Cite this article

Abstract

Activation-induced cytidine deaminase (AID) is essential for somatic hypermutation of B-cells. We investigated the expression of AID mRNA by real-time polymerase chain reaction (PCR) in peripheral blood mononuclear cells of 80 patients with B-CLL. AID expression was detected in 45 of 80 patients (56%) at various levels, but was undetectable in 35 patients (44%). AID PCR positivity was associated with unmutated IGVH gene status (22 of 25 patients; P=0.002) and unfavourable cytogenetics (18 of 23 patients with deletion in 11q or loss of p53; P=0.040). Using a threshold level of 0.01-fold expression compared to Ramos control cells, even more significant associations were observed (P=0.001 for IGVH; P=0.002 for cytogenetics). A correlation was observed between individual AID levels and the percentage of VH homology (R=0.41; P=0.001). AID positivity predicted unmutated IGVH status with an odds ratio of 8.31 (P=0.003) and poor risk cytogenetics with an odds ratio of 3.46 (P=0.032). Significance was retained after adjustment for Binet or Rai stages. AID mRNA levels were stable over time. These data suggest a potential role of AID as a prognostic marker in B-CLL.

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Acknowledgements

We wish to thank Bernd Biermayer for IGVH sequence analysis and Uli Zeman for excellent technical assistance and Zahida Chaudary for documentation of patients enrolled in GCLLSG studies. This work was supported by the Austrian National Bank Grant # 9964, by the Center of Molecular Medicine (CeMM) of the Austrian Academy of Sciences (#20010) (UJ, DH), by Sander Stiftung Grant # 2001.004.1, and by BMBF Grant # 01KW9934 (SS, HD).

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Authors and Affiliations

  1. Department of Internal Medicine I, Division of Hematology and Hemostaseology, University of Vienna, Austria

    D Heintel, J Schwarzmeier, T Le, A Gaiger & U Jäger

  2. Department of Medical Biology, University of Vienna, Austria

    E Kroemer & C Fonatsch

  3. Department of Internal Medicine III, University of Ulm, Germany

    D Kienle, S Stilgenbauer & H Döhner

  4. Department of Clinical Chemistry and Laboratory Medicine, University of Vienna, Austria

    I Schwarzinger, R Marculescu & C Mannhalter

  5. Department of Medical Computer Sciences, Section of Clinical Biometrics, University of Vienna, Austria

    A Gleiß

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Heintel, D., Kroemer, E., Kienle, D. et al. High expression of activation-induced cytidine deaminase (AID) mRNA is associated with unmutated IGVH gene status and unfavourable cytogenetic aberrations in patients with chronic lymphocytic leukaemia. Leukemia 18, 756–762 (2004). https://doi.org/10.1038/sj.leu.2403294

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