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Molecular Cytogenetics

Cryptic t(4;11) encoding MLL-AF4 due to insertion of 5′ MLL sequences in chromosome 4

Leukemia volume 15, pages 595–600 (2001)Cite this article

Abstract

The t(4;11) translocation is the cytogenetic hallmark of a subset of acute lymphoblastic leukemias characterized by pro-B immunophenotype and a dismal prognosis. This translocation fuses the MLL gene on chromosome band 11q23 and the AF4 gene on 4q21, resulting in the expression of fusion transcripts from both translocated chromosomes. The MLL-AF4 chimeric transcript is thought to mediate the leukemic transformation. The MLL genomic disruption detected by Southern blot and the RT-PCR for the MLL-AF4 chimeric transcript expression are molecular evidence of this chromosomal translocation. However, similar molecular rearrangements have also been identified in cases without the cytogenetic t(4;11). We report a 30-year-old patient with high risk ALL, a normal karyotype, and molecular evidence of MLL-AF4 fusion. Using a double color FISH assay with MLL specific PAC probes, a cryptic t(4;11) due to insertion of 5′ MLL sequences in chromosome 4q21 was demonstrated. Consequently the MLL-AF4 was encoded by der(4). This insertion mechanism precludes the genomic recombination of AF4-MLLand supports the crucial role played by MLL-AF4 in leukemogenesis. The findings of our case, along with others, show the importance of complementing the karyotype with molecular and FISH techniques.

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Acknowledgements

This text presents the research results of the Belgian programme on Interuniversity Poles of Attraction initiated by the Belgian State, Prime Minister's Office, Science Policy Programming. The scientific responsibility is assumed by the authors. The work was supported by the Flemish Government in the frame of the action ‘Kom op tegen Kanker/Vlaamse Kankerliga’ and the IRS/JA Cohen Institute (Grant No. 6.3.4). The authors thank B Emanuel, R Logist, Dr Y Beguin and Dr C Herens for technical support, clerical assistance and providing clinical and cytogenetic follow-up data, respectively, and also Dr M Reichel and Dr O Haas for providing the AF4 PAC clone.

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Authors and Affiliations

  1. Department of Pathology, Leiden University Medical Center, The Netherlands

    A von Bergh, Ph Kluin & E Schuuring

  2. Center for Human Genetics, Catholic University of Leuven, Leuven, Belgium

    P Gargallo, H Vranckx & A Hagemeijer

  3. Department of Genetics, Instituto de Investigaciones Hematologicas de la Academia Nacional de Medicina de Buenos Aires, Argentina

    P Gargallo & I Larripa

  4. CHR de la Citadelle, Liège, Belgium

    B De Prijck

  5. Department of Genetics, University of Erlangen-Nuernberg, Germany

    R Marschalek

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  1. A von Bergh
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von Bergh, A., Gargallo, P., De Prijck, B. et al. Cryptic t(4;11) encoding MLL-AF4 due to insertion of 5′ MLL sequences in chromosome 4. Leukemia 15, 595–600 (2001). https://doi.org/10.1038/sj.leu.2402050

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