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MLL rearrangements emerge during spontaneous apoptosis of clinical blood samples

Leukemia volume 20, pages 1193–1194 (2006)Cite this article

The MLL gene (11q23) is frequently involved in genetic aberrations in de novo and therapy-related acute myeloid leukemia (t-AML). In t-AML, MLL translocations are detectable in up to 10% of all cases.1 Typically, these t-AML are characterized by a short latency period of up to 2 years and are associated with previous topoisomerase inhibitor treatment.2 The initiating event is thought to be a breakage at the topoisomerase binding site within the breakpoint cluster region (bcr; exons 5–11) of the MLL gene. In more than 70% of MLL-positive t-AML, the MLL breakpoint is localized in the telomeric region of the bcr, whereas in de novo AML, it is in the centromeric region.3 MLL aberrations (deletions, insertions, translocations) can be induced in normal hematopoietic progenitors in vitro by exposure to topoisomerase II inhibitors,4 and by retrospective analysis, t-AML-associated MLL aberrations have been backtracked up to a few months after topoisomerase II inhibitor therapy in clinical samples.5

As the incidence of t-AML may be up to 10% in high-dose, myeloablative treatment schedules, it is of certain interest to identify patients who are at an increased risk to attract this complication. Recently, Ng et al.6 investigated clinical samples of children who were treated with topoisomerase inhibitors/anthracyclines by Southern blot and panhandle PCR and observed MLL aberrations (MLL breakage and illegitimate recombination) in 7% (5/71) of the patients.

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References

  1. Schoch C, Schnittger S, Klaus M, Kern W, Hiddemann W, Haferlach T . AML with 11q23/MLL abnormalities as defined by the WHO classification: incidence, partner chromosomes, FAB subtype, age distribution, and prognostic impact in an unselected series of 1897 cytogenetically analyzed AML cases. Blood 2003; 102: 2395–2402.

    Article  CAS  Google Scholar 

  2. Pedersen-Bjergaard J . Insights into leukemogenesis from therapy-related leukemia. N Engl J Med 2005; 352: 1591–1594.

    Article  CAS  Google Scholar 

  3. Super HJ, McCabe NR, Thirman MJ, Larson RA, Le Beau MM, Pedersen-Bjergaard J et al. Rearrangements of the MLL gene in therapy-related acute myeloid leukemia in patients previously treated with agents targeting DNA–topoisomerase II. Blood 1993; 82: 3705–3711.

    CAS  PubMed  Google Scholar 

  4. Libura J, Slater DJ, Felix CA, Richardson C . Therapy-related acute myeloid leukemia-like MLL rearrangements are induced by etoposide in primary human CD34+ cells and remain stable after clonal expansion. Blood 2005; 105: 2124–2131.

    Article  CAS  Google Scholar 

  5. Megonigal MD, Cheung NK, Rappaport EF, Nowell PC, Wilson RB, Jones DH et al. Detection of leukemia-associated MLL-GAS7 translocation early during chemotherapy with DNA topoisomerase II inhibitors. Proc Natl Acad Sci USA 2000; 97: 2814–2819.

    Article  CAS  Google Scholar 

  6. Ng A, Taylor GM, Wynn RF, Eden OB . Effects of topoisomerase 2 inhibitors on the MLL gene in children receiving chemotherapy: a prospective study. Leukemia 2005; 19: 253–259.

    Article  CAS  Google Scholar 

  7. Stanulla M, Wang J, Chervinsky DS, Thandla S, Aplan PD . DNA cleavage within the MLL breakpoint cluster region is a specific event which occurs as part of higher-order chromatin fragmentation during the initial stages of apoptosis. Mol Cell Biol 1997; 17: 4070–4079.

    Article  CAS  Google Scholar 

  8. Betti CJ, Villalobos MJ, Jiang Q, Cline E, Diaz MO, Loredo G et al. Cleavage of the MLL gene by activators of apoptosis is independent of topoisomerase II activity. Leukemia 2005; 19: 2289–2295.

    Article  CAS  Google Scholar 

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  1. J Basecke and F Griesinger: This work was supported by the German Hector-Stiftung (grant M18).

Authors and Affiliations

  1. Department of Hematology and Oncology, University of Goettingen, Goettingen, Germany

    J Basecke, K Karim, M Podleschny, A Becker, B Glass, L Trumper & F Griesinger

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  1. J Basecke
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  2. K Karim
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Basecke, J., Karim, K., Podleschny, M. et al. MLL rearrangements emerge during spontaneous apoptosis of clinical blood samples. Leukemia 20, 1193–1194 (2006). https://doi.org/10.1038/sj.leu.2404211

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