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Molecular identification of CBFβ-MYH11 fusion transcripts in an AML M4Eo patient in the absence of inv16 or other abnormality by cytogenetic and FISH analyses – a rare occurrence

Leukemia volume 17, pages 1907–1910 (2003)Cite this article

The prognostic and therapeutic significance of karyotype at diagnosis in patients with AML is now fully established. Two of the most common recurring cytogenetic abnormalities in AML are t(8;21)(q22;q22) and the pericentric inversion of chromosome 16, inv(16)(p13;q22), or its variant t(16;16)(p13;q22). The chromosome 16 abnormalities, which are closely associated with the FAB subtype M4Eo, result in the creation of a fusion gene between the smooth muscle myosin-heavy chain gene (MYH11) at 16p13 and the core binding factor β (CBFβ) gene at 16q22. The fusion protein product, CBFβ-MYH11, interacts with nuclear corepressors, leading to dysregulation of transcription. Patients with ‘CBF leukemias’ including those with inv(16)/t(16;16) account for up to 20% of young adult cases of de novo AML. Such patients have a more favorable prognosis, particularly when treated with intensive postremission therapy including high-dose cytarabine. Therefore, accurate identification of these patients at diagnosis is of therapeutic significance.

Several recent reports have examined the utility of cytogenetics, FISH, and molecular analyses to detect CBFβ–MYH11 fusion transcripts in patients with AML.1,2,3,4,5,6,7 In initial reports, patients expressing the CBFβ–MYH11 chimeric gene in the absence of chromosome 16 aberrations were reported to account for up to 43% of all molecularly positive patients.2,3,4 Other studies have reported a much lower incidence of such discordance between cytogenetic and molecular analyses.1,5,6,7 These discrepancies may be a consequence of the difficulty in detecting the inv(16) cytogenetically.8 In all these reports, the expression of CBFβ–MYH11 fusion transcripts in the presence of a normal karyotype without chromosome 16 abnormalities and other cytogenetic aberrations was rare. In the studies providing information on the number of patients with a normal karyotype, the incidence of molecularly positive disease was 1.5% (one of 65),2 1.1% (one of 87),7 and 0.8% (one of 124)1. In the latter study, the single patient initially reported as having a normal karyotype was found to have inv(16) on re-examination.1 In the study of 412 patients by Rowe et al.,5 no instances of a positive PCR result without a cytogenetically detectable chromosome 16 aberration were reported. Ritter et al4 reported three such patients with normal cytogenetics and the presence of the fusion gene by molecular analysis.

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Acknowledgements

The expert technical assistance of Andrew Miner is gratefully acknowledged. We also thank Drs K Richkind and P Rushton of Genzyme Genetics for their kind contribution of Figure 1a. F Ravandi and SS Kadkol contributed equally to this work.

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  1. Departments of Medicine, University of Illinois at Chicago, Chicago, IL, USA

    F Ravandi & J Ridgeway

  2. Departments of Pathology, University of Illinois at Chicago, Chicago, IL, USA

    S S Kadkol, A Bruno, C Dodge & V Lindgren

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Ravandi, F., Kadkol, S., Ridgeway, J. et al. Molecular identification of CBFβ-MYH11 fusion transcripts in an AML M4Eo patient in the absence of inv16 or other abnormality by cytogenetic and FISH analyses – a rare occurrence. Leukemia 17, 1907–1910 (2003). https://doi.org/10.1038/sj.leu.2403056

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