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Role of the TEL-AML1 fusion gene in the molecular pathogenesis of childhood acute lymphoblastic leukaemia

Oncogene volume 23, pages 4275–4283 (2004)Cite this article

Abstract

Balanced chromosomal translocations are frequently associated with haematopoietic neoplasms and often involve genes that encode transcription factors, which play critical roles in normal haematopoiesis. Fusion oncoproteins that arise from chimeric genes generated by such translocations are usually stable and consistent molecular markers for a given disease subtype and contribute to the leukaemogenic processes. The t(12;21)(p13;q22) chromosomal translocation is the most frequent illegitimate gene recombination in paediatric cancer, occurring in approximately 25% of common (c) B-cell precursor acute lymphoblastic leukaemia (cALL) cases. The rearrangement results in the in-frame fusion of the 5′ region of the ETS-related gene, TEL (ETV6), to almost the entire AML1 (RUNX1) locus and is associated with favourable prognosis following conventional therapeutic strategies. We discuss here the prenatal origins of the TEL/AML1 translocation as an initiating mutation, the role of TEL-AML1 in cellular transformation and the molecular mechanisms by which the chimeric protein imposes altered patterns of gene expression.

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Acknowledgements

We are grateful to the Leukaemia Research Fund of Great Britain (A.Z., M.G., T.E.) and Medical Research Council, UK (T.E.) for support.

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  1. Section of Haematological Oncology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK

    Arthur Zelent & Mel Greaves

  2. MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK

    Tariq Enver

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Correspondence to Arthur Zelent.

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Zelent, A., Greaves, M. & Enver, T. Role of the TEL-AML1 fusion gene in the molecular pathogenesis of childhood acute lymphoblastic leukaemia. Oncogene 23, 4275–4283 (2004). https://doi.org/10.1038/sj.onc.1207672

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