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A novel exon in AML1-ETO negatively influences the clonogenic potential of the t(8;21) in acute myeloid leukemia

Leukemia volume 24, pages 891–894 (2010)Cite this article

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The t(8;21) (q22;q22) is a common translocation in acute myeloid leukemia (AML). In this translocation the AML1 (RUNX1) gene coding for a DNA-binding domain, is fused to most of the ETO (RUNX1T1) gene, which encodes four nervy homology regions (NHRs) that function as repressors of transcription. The resulting fusion gene AML1-ETO (RUNX1-RUNX1T1), which gives rise to a major transcript coding for a product of 752 amino acids (aa), is alone insufficient to cause leukemia in animal models; suggesting additional genetic aberrations are required to achieve full leukemic potential. However, studies have shown alternative transcripts of AML1-ETO to be co-expressed alongside the full-length transcript.1 These transcripts often occur as a result of alternative exon usage and importantly appear to have a role in the leukemogenic capabilities of this translocation. For example, the utilization of the alternative ETO exon 9a results in a truncated AML1-ETO product of 552 aa lacking the NHR3 and NHR4 domains and whose expression in mouse models leads to the rapid development of leukemia.2

Our aim was to analyze further alternative transcripts of AML1-ETO. Our discoveries have revealed further exons and alternative transcripts of AML1-ETO whose clonogenic potential has been assessed.

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Author notes

  1. D Gascoyne

    Present address: Current address: Nuffield Department of Clinical Lab Sciences, University of Oxford, Oxford, UK

Authors and Affiliations

  1. Medical Oncology Laboratory, Cancer Genomics Group, Barts and The London School of Medicine, London, UK

    D Mannari, J Dunne, T Chaplin & B Young

  2. Molecular Haematology and Cancer Biology Unit, Institute of Child Health, UCL, London, UK

    D Gascoyne

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  1. D Mannari
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  2. D Gascoyne
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  3. J Dunne
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Correspondence to D Mannari.

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Supplementary Information accompanies the paper on the Leukemia website

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Mannari, D., Gascoyne, D., Dunne, J. et al. A novel exon in AML1-ETO negatively influences the clonogenic potential of the t(8;21) in acute myeloid leukemia. Leukemia 24, 891–894 (2010). https://doi.org/10.1038/leu.2009.288

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