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Characterization of t(12;21) breakpoint junctions in acute lymphoblastic leukemia

Leukemia volume 15, pages 858–859 (2001)Cite this article

The t(12;21)(p13;q22) translocation is the most frequent chromosomal abnormality associated with pediatric B cell precursor acute lymphoblastic leukemia (ALL). The translocation partners are the TEL and AML1 genes on chromosome 12 and 21, respectively. The majority of t(12;21) translocations occur in TEL intron 5 and AML1 intron 1, resulting in fusion of TEL exons 1–5 and AML1 exons 2–8.1 The rearrangement process involved in the translocations has been explained by mistakes in normal V(D)J recombinase activity, homologous recombination between repeated sequences or fusion between staggered double-strand DNA. We have conducted analyses of the chromosomal breakpoint regions in DNA from nine ALL patients carrying the t(12;21) translocation to describe the molecular mechanisms of the rearrangement process.

The source of DNA was mononuclear cells isolated by Ficoll density centrifugation from peripheral blood or bone marrow at the time of diagnosis. Genomic DNA was isolated using a standard SDS/proteinase K/phenol extraction method. To identify the breakpoint regions, we performed long distance inverse PCR (LDI-PCR) analyses essentially as described by Willis et al2 using the Expand 20 kbplus PCR System (Roche, Mannheim, Germany) and primers described by Wiemels et al.1 PCR conditions were: 92°C for 2 min; 30 cycles of: (92°C for 10 s; 62°C for 30 s; 68°C for 14 min) and 68°C for 7 min. PCR products were extracted using phenol:chloroform (pH 8.0) and the DNA sequence determined.

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Acknowledgements

We thank Claus Bus and Dorthe Caroline Riishøj for technical assistance. This study was supported by grants from the Danish Cancer Society (98 100 31, 98 100 32, 19 500 06 and 99 144 08 9132), the Danish Natural Science Research Council (99 018 46), and the Karen Elise Jensen Foundation.

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Authors and Affiliations

  1. Department of Molecular and Structural Biology, University of Aarhus, Aarhus, Denmark

    MT Andersen, I Nordentoft, CL Christiansen, VD Jakobsen & P Jørgensen

  2. Department of Epidemiology Research, Danish Epidemiology Science Centre, Copenhagen, Denmark

    LL Hjalgrim, H Hjalgrim & M Melbye

  3. Department of Haematology and Medicine, Aarhus University Hospital, Aarhus, Denmark

    N Pallisgaard & P Hokland

  4. Department of Clinical Immunology, Tissue Typing Laboratory, The Juliane Marie Centre, National University Hospital, Copenhagen, Denmark

    HO Madsen & LP Ryder

  5. Department of Clinical Biochemistry, Statens Serum Institutz, Copenhagen, Denmark

    M Christiansen

  6. Department of Pediatrics, University Hospital of Aarhus at Skejby, Denmark

    N Clausen

  7. Pediatric Clinic II, The Juliane Marie Centre, National University Hospital, Copenhagen, Denmark

    K Schmiegelow

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  1. MT Andersen
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Andersen, M., Nordentoft, I., Hjalgrim, L. et al. Characterization of t(12;21) breakpoint junctions in acute lymphoblastic leukemia. Leukemia 15, 858–859 (2001). https://doi.org/10.1038/sj.leu.2402095

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  • DOI: https://doi.org/10.1038/sj.leu.2402095

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