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Oncogenes, Fusion Genes and Tumor Suppressor Genes

New insights to the MLL recombinome of acute leukemias

Leukemia volume 23, pages 1490–1499 (2009)Cite this article

Abstract

Chromosomal rearrangements of the human MLL gene are associated with high-risk pediatric, adult and therapy-associated acute leukemias. These patients need to be identified, treated appropriately and minimal residual disease was monitored by quantitative PCR techniques. Genomic DNA was isolated from individual acute leukemia patients to identify and characterize chromosomal rearrangements involving the human MLL gene. A total of 760 MLL-rearranged biopsy samples obtained from 384 pediatric and 376 adult leukemia patients were characterized at the molecular level. The distribution of MLL breakpoints for clinical subtypes (acute lymphoblastic leukemia, acute myeloid leukemia, pediatric and adult) and fused translocation partner genes (TPGs) will be presented, including novel MLL fusion genes. Combined data of our study and recently published data revealed 104 different MLL rearrangements of which 64 TPGs are now characterized on the molecular level. Nine TPGs seem to be predominantly involved in genetic recombinations of MLL: AFF1/AF4, MLLT3/AF9, MLLT1/ENL, MLLT10/AF10, MLLT4/AF6, ELL, EPS15/AF1P, MLLT6/AF17 and SEPT6, respectively. Moreover, we describe for the first time the genetic network of reciprocal MLL gene fusions deriving from complex rearrangements.

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Acknowledgements

This work was made possible by and conducted within the framework of the International BFM Study Group. This study was supported by grant 107819 from the Deutsche Krebshilfe to RM, TD and TK; supported by grant R06/22 from the German José Carreras Leukemia foundation to TB and supported by grant 2 P054 095 30 from the Polish Ministry of Science and Higher Education to TS.

Author information

Authors and Affiliations

  1. Diagnostic Center of Acute Leukemia, Institute of Pharmaceutical Biology, ZAFES, University of Frankfurt, Frankfurt/Main, Germany

    C Meyer, E Kowarz, J Hofmann, T Dingermann & R Marschalek

  2. Department of Hematology, Biology and Pathology Center, CHU of Lille, Lille, France

    A Renneville

  3. INSERM, U-837, Team 3, Lille, France

    A Renneville

  4. Department of Paediatric Haematology/Oncology, CLIP, Second Faculty of Medicine, Charles University Prague, Prague, Czech Republic

    J Zuna & J Trka

  5. Biological Hematology, AP-HP Necker, UniversitéParis Descartes, Paris, France

    R Ben Abdelali & E Macintyre

  6. Faculté de Médecine et des Sciences de la Santé, Laboratoire d'Histologie, Embryologie et Cytogénétique, Université de Bretagne Occidentale, Brest, France

    E De Braekeleer & M De Braekeleer

  7. INSERM-U613, Brest, France

    E De Braekeleer & M De Braekeleer

  8. CHU Purpan, Laboratoire d’Hématologie, Toulouse, France

    E Delabesse

  9. Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Cancer Rio de Janeiro, Rio de Janeiro, Brazil

    M P de Oliveira

  10. Département de Génétique, Hopital Robert Debré, Paris, France

    H Cavé & E Clappier

  11. Department of Immunology, Erasmus MC, Sophia Children's Hospital, Rotterdam, The Netherlands

    J J M van Dongen

  12. Department of Pediatric Oncology/Hematology, Erasmus MC, Sophia Children's Hospital, Rotterdam, The Netherlands

    B V Balgobind & M M van den Heuvel-Eibrink

  13. Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands

    H B Beverloo

  14. Children's Cancer Research Institute, Vienna, Austria

    R Panzer-Grümayer & S Strehl

  15. Department of Pediatric Hematology and Oncology, Children's University Hospital, Giessen, Germany

    A Teigler-Schlegel & J Harbott

  16. Cancercytogenetics Laboratory, Aarhus University Hospital, Aarhus, Denmark

    E Kjeldsen

  17. MLL Munich Leukemia Laboratory, Munich, Germany

    S Schnittger

  18. Department of Pediatric Hematology and Oncology, University of Frankfurt, Frankfurt/Main, Germany

    U Koehl & T Klingebiel

  19. Department of Pediatrics, University of Jena, Jena, Germany

    B Gruhn

  20. Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK

    O Heidenreich

  21. Department of Pathology, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China

    L C Chan & S F Yip

  22. Canada's Michael Smith Genome Sciences Center, Vancouver, British Columbia, Canada

    M Krzywinski

  23. Department of Pediatric Oncology and Hematology, Charité Medical University Berlin, CVK, Berlin, Germany

    C Eckert

  24. Department of Paediatrics, University of Schleswig-Holstein, Kiel, Germany

    A Möricke & M Schrappe

  25. Servcio de Hemato-Oncología, Hospital Nacional de Pediatría Prof Dr JP Garrahan, Buenos Aires, Argentina

    C N Alonso

  26. Department of Oncology, University Children's Hospital, Zurich, Switzerland

    B W Schäfer

  27. Clinic for Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hanover Medical School, Hanover, Germany

    J Krauter

  28. Division of Pediatrics, Cell Therapy Section, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    D A Lee

  29. Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    U zur Stadt

  30. Department of Paediatrics and Oncohematology, University of Padua, Padua, Italy

    G Te Kronnie

  31. Sydney Children's Hospital, Children's Cancer Institute, Sydney, New South Wales, Australia

    R Sutton

  32. Department of Pediatric Hemato-Oncology, The Chaim Sheba Medical Center, Tel Aviv, Israel

    S Izraeli & L Trakhtenbrot

  33. The Cancer Research Center, Tel Aviv, Israel

    S Izraeli & L Trakhtenbrot

  34. Sackler Medical School Tel Aviv University, Tel Aviv, Israel

    S Izraeli & L Trakhtenbrot

  35. Center of Pediatric Hematology Oncology, University of Catania, Catania, Italy

    L Lo Nigro

  36. Regional Children Hospital 1, Pediatric Oncology and Hematology Center, Research Institute of Medical Cell Technologies, Ekaterinburg, Russia

    G Tsaur & L Fechina

  37. Department of Pediatric Hematology and Oncology, Medical University of Silesia, Zabrze, Poland

    T Szczepanski

  38. Department of Clinical Genetics, National Cancer Hospital, Bratislava, Slovakia

    D Ilencikova

  39. Medical Faculty III, CBF, Charité Medical University Berlin, Berlin, Germany

    M Molkentin & T Burmeister

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  1. C Meyer
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  2. E Kowarz
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Correspondence to R Marschalek.

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Meyer, C., Kowarz, E., Hofmann, J. et al. New insights to the MLL recombinome of acute leukemias. Leukemia 23, 1490–1499 (2009). https://doi.org/10.1038/leu.2009.33

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Keywords

  • MLL
  • translocations partner genes
  • acute leukemia
  • ALL
  • AML

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