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Molecular Cytogenetics

Detection of E2A translocations in leukemias via fluorescence in situ hybridization

Leukemia volume 15, pages 95–102 (2001)Cite this article

Abstract

Three rearrangements in ALL disrupt E2A and create E2A fusion proteins: the t(1;19)(q23;p13) and E2A-PBX1, t(17;19)(q22;p13) and E2A-HLF and a cryptic inv(19)(p13;q13) and E2A-FB1. While E2A is fused to PBX1 in most ALLs with a t(1;19), 5–10% of cases have translocations that appear identical, but do not affect E2A or PBX1. Because more intensive therapy improves the outcome of patients with E2A-PBX1positive (1;19) translocations, it is critical to identify this subset of patients so that appropriate therapy can be administered. In addition, there are balanced and unbalanced variants of the t(1;19) and controversy exists regarding the clinical significance of this distinction. We have developed a two-color fluorescence in situhybridization assay that accurately detects E2A translocations in metaphase and interphase cells, distinguishes between balanced and unbalanced variants and identifies patients with a t(1;19) who lack E2A-PBX1 fusion. We found that clonal microheterogeneity is common in patients with E2A translocations and most patients have mixtures of cells with balanced and unbalanced translocations, suggesting that this distinction represents two ends of a continuum rather than distinct biological entities. These reagents should have widespread clinical utility and be useful for translational and basic research studies involving E2Atranslocations and this region of chromosome 19p13.

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Acknowledgements

This work was supported by grants from the Loewenstern and Monfort Family Foundations to SPH and NCI Cancer Center Core Grant CA 46934. SPH is a Translational Research Grant Awardee of the Leukemia and Lymphoma Society of America. Work at LLNL was performed under the auspices of the US DOE under contract No. W-7405-ENG-48.

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Authors and Affiliations

  1. Department of Pediatrics, Section of Pediatric Hematology/Oncology, USA

    T Boomer, M Varella-Garcia & SP Hunger

  2. University of Colorado Cancer Center, Denver, CO, USA

    T Boomer, L McGavran & SP Hunger

  3. Department of Internal Medicine, University of Colorado School of Medicine, USA

    M Varella-Garcia

  4. Department of Pathology, University of Colorado School of Medicine, USA

    L McGavran & L Meltesen

  5. Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, CA, USA

    AS Olsen

  6. The Children's Hospital, USA

    SP Hunger

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  1. T Boomer
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Boomer, T., Varella-Garcia, M., McGavran, L. et al. Detection of E2A translocations in leukemias via fluorescence in situ hybridization. Leukemia 15, 95–102 (2001). https://doi.org/10.1038/sj.leu.2401988

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  • DOI: https://doi.org/10.1038/sj.leu.2401988

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