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Arbitration and Interpretation

Screening for core binding factor gene rearrangements in acute myeloid leukemia

Leukemia volume 16, pages 964–969 (2002)Cite this article

Genes encoding the core binding factor (CBF) α2 (AML1, RUNX1) and β subunits are amongst the commonest targets of chromosomal rearrangements in acute myeloid leukemia (AML), which include t(8;21)(q22;q22) and inv(16)(p13q22)/t(16;16)(p13;q22), leading to formation of AML1-ETO and CBFβ-MYH11 fusion genes, respectively (reviewed in Friedman1). AML cases with t(8;21) and inv(16)/ t(16;16) have been found to have a relatively favorable prognosis, characterized by high complete remission rates associated with low levels of resistant disease and superior overall survival.2,3,4 Recent studies suggest that this subgroup of AML, which is recognized by the recent WHO classification,5 demands a specific treatment approach. In particular, bone marrow transplantation (BMT) has been shown to confer no overall survival advantage in such cases,6,7 which may, however, particularly benefit from high-dose ara-C as consolidation therapy.8

Over the last few years it has become apparent that a proportion of AML cases have an underlying AML1-ETO or CBFβ-MYH11 fusion gene in the apparent absence of the classic t(8;21) or inv(16)/t(16;16), respectively.9,10,11,12,13,14,15,16 There are a number of potential reasons for this, which may be classified into the following subgroups:

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Acknowledgements

I am indebted to Marina Lafage-Pochitaloff, Nicole Dastugue, Stephen Langabeer, Helen Walker and David Linch for helpful comments and to the Leukaemia Research Fund of Great Britain for support. I thank David Rowe, Margit Mitterbauer and Ulrich Jaeger for provision of additional clinical data relating to their published studies.

Leukemia favours critical exchanges of views. We received a commentary from Dr David Rowe on a paper published in Leukemia 2001; 15: 57–61. As usual, the authors to whom the commentary was addressed were invited to reply. I am most indebted to Dr David Grimwade, who accepted to be the mediator in this exchange of interpretation of data. Not only did Dr Grimwade monitor this small debate but he also, in a most constructive fashion, contributed to it himself with a balanced view on the question in point. This is what is presented here.

Nicole Muller-Bérat, MD, Editor-in-Chief

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  1. Division of Medical and Molecular Genetics, Guy's, King's and St Thomas’ School of Medicine and Dept of Haematology, University College London Hospitals, London, UK

    D Grimwade

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Grimwade, D. Screening for core binding factor gene rearrangements in acute myeloid leukemia. Leukemia 16, 964–969 (2002). https://doi.org/10.1038/sj.leu.2402421

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