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Acute Leukemias

Monitoring minimal residual disease by quantification of genomic chromosomal breakpoint sequences in acute leukemias with MLL aberrations

Leukemia volume 20, pages 451–457 (2006)Cite this article

Abstract

An estimated 10% of acute leukemias carry mixed-lineage leukemia (MLL) fusion genes. Approximately 50 different fusion partners of the MLL gene have already been molecularly identified. These leukemias are commonly regarded as high-risk cases and are treated accordingly with intensified therapy regimens, including hematopoietic stem cell transplantation. However, a subset of patients may achieve long-term remissions with conventional therapy. Monitoring minimal residual disease (MRD) is undoubtedly of great value in clinical decision making, also in the pre- and post-transplant setting. Here, we describe a novel method for detecting MRD in leukemias with MLL aberrations. The method is based on monitoring patient-specific chromosomal breakpoint DNA sequences. This has several advantages over other methods that are based either on detecting specific RNA molecules of MLL fusion genes or on surrogate markers. An accurate and absolute quantification of the MRD level is possible. No reference to housekeeping genes is necessary and the target structure is much more stable than any mRNA fusion transcript.

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Acknowledgements

We thank all participating clinics of the GMALL therapy study for their support. We are particularly indebted to Ms M Molkentin (Berlin) for skilful PCR analysis, and Ms B Komischke and R Lippoldt (both Berlin) for immunophenotyping. Grant numbers and sources of support: Grant 10-1988-Bu1 (Deutsche Krebshilfe) to TB and SS, grant 70-2657-Ho2 (Deutsche Krebshilfe) to DH and ET, grant 2002.032.1 (Wilhelm Sander Stiftung) to RM.

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Authors and Affiliations

  1. Medizinische Klinik III, Campus Benjamin Franklin, Charité Universitätsmedizin Berlin, Hindenburgdamm 30, Berlin, Germany

    T Burmeister, S Schwartz & E Thiel

  2. Institut für Pharmazeutische Biologie/ZAFES/Diagnostikzentrum für Akute Leukämie (DCAL), Johann Wolfgang Goethe-Universität, Marie-Curie Str. 9, Frankfurt/Main, Germany

    R Marschalek, B Schneider & C Meyer

  3. Medizinische Klinik III, Johann Wolfgang Goethe-Universität, Theodor Stern-Kai 7, Frankfurt/Main, Germany

    N Gökbuget & D Hoelzer

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  1. T Burmeister
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Correspondence to T Burmeister.

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

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Burmeister, T., Marschalek, R., Schneider, B. et al. Monitoring minimal residual disease by quantification of genomic chromosomal breakpoint sequences in acute leukemias with MLL aberrations. Leukemia 20, 451–457 (2006). https://doi.org/10.1038/sj.leu.2404082

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