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Reported cryptic rearrangements of CBFβ-MYH11 in acute myeloid leukaemia are not due to false priming of contaminating DNA

Leukemia volume 14, pages 944–945 (2000)Cite this article

The presence of inv(16)(p13q22) at diagnosis of acute myeloid leukaemia (AML) is one of several good prognostic, cytogenetic indicators,1 and such cytogenetic data are now used to stratify patient therapy (eg UK MRC AML 12 trial). The inv(16) chromosomal abnormality results in disruption of the CBFβ gene and creation of the CBFβ-MYH11 fusion gene.2 Transcripts from this fusion gene can be detected by RT-PCR and several groups, including ourselves, have shown that PCR techniques not only confirm positive cytogenetic findings for inv(16) but also allow detection of additional cases in which this translocation is not apparent.34567 In some cases, this is because the inv(16) abnormality is subtle and only detectable in good metaphase preparations, but in most cases these cryptic rearrangements are undetectable by high quality conventional cytogenetics. This finding has led us to suggest that all cases of AML should be screened for the presence of CBFβ-MYH11 fusion transcripts (and AML1-ETO transcripts).38

Recently Hackwell et al9 reported a very high proportion of ‘false positive’ results using the primer sets from our study. They demonstrated that this is due to the 5′ nested CBFβ primer cross-hybridising with an intronic sequence of contaminating MYH11 genomic DNA, which results in the amplification of a 210 bp sequence from DNA of similar size to the expected 209 bp CBFβ-MYH11 RT-PCR product. This raised the possibility that the cryptic rearrangements reported by ourselves were spurious, and for this reason we have re-analysed 10 out of the 12 cases of cryptic rearrangement that we previously described. In the other two cases, there was no RNA for further analysis.

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Acknowledgements

This work was supported by the Kay Kendall Leukaemia Fund.

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  1. Department of Haematology, University College London Medical School, London, UK

    SE Langabeer, RE Gale, H Walker & DC Linch

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  1. SE Langabeer
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Langabeer, S., Gale, R., Walker, H. et al. Reported cryptic rearrangements of CBFβ-MYH11 in acute myeloid leukaemia are not due to false priming of contaminating DNA. Leukemia 14, 944–945 (2000). https://doi.org/10.1038/sj.leu.2401751

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