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Cytogenetics and Molecular Genetics

Rare CBFB-MYH11 fusion transcripts in AML with inv(16)/t(16;16) are associated with therapy-related AML M4eo, atypical cytomorphology, atypical immunophenotype, atypical additional chromosomal rearrangements and low white blood cell count: a study on 162 patients

Leukemia volume 21, pages 725–731 (2007)Cite this article

Abstract

The spectrum of CBFB-MYH11 fusion transcripts in acute myeloid leukemia (AML) M4eo with inv(16)/t(16;16) is heterogeneous. Approximately 85% show type A CBFB-MYH11 fusion transcripts. In addition, more than 10 different fusion transcripts have been reported. The prognostic impact and biological background of rare fusion transcripts remain open. In this study, a molecular characterization of CBFB-MYH11 transcripts in 162 patients with CBFB-MYH11 positive AML at diagnosis was performed. In total, 128 patients (79.0%) showed the fusion transcript type A, whereas nine different rare CBFB-MYH11 fusion genes were detected in 34 cases (21.0%). Rare fusion transcripts were found more frequently in therapy-related AML (P=0.0106). Numerical gains of the chromosomes 8, 21 and 22 were more frequently associated with type A (28.3%) than with rare fusions (12.9%) (P=0.012). Median white blood cell (WBC) count was higher in type A (35.4 G/l; range=1.1–279 G/l) than in cases with rare types (7.8 G/l; range=0.8–148.0 G/l) (P<0.0001). Rare fusion transcripts were correlated with an atypical cytomorphology not primarily suggestive for the FAB subtype M4eo (P=0.0203). Immunophenotype revealed lower CD2, CD13, CD33 and CD90 levels than in type A fusion cases (P=0.036, 0.002, 0.029 and 0.045, respectively). However, the type of fusion was not an independent prognostic parameter.

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Acknowledgements

This investigation was performed in part in the Laboratory for Leukemia Diagnostics; Medical Department III, (Head: Professor Dr W Hiddemann), Ludwig-Maximilians-University, Munich. We thank all participants of the AMLCG study group for sending bone marrow or blood samples to our laboratory for reference diagnosis and for submitting clinical data, as part of the patients were treated within the AMLCG study group.

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Authors and Affiliations

  1. MLL Munich Leukemia Laboratory, Munich, Germany

    S Schnittger, C Haferlach, W Kern & T Haferlach

  2. Department of Clinical Chemistry, Ludwig-Maximilians-University, Munich, Germany

    U Bacher

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Correspondence to S Schnittger.

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Schnittger, S., Bacher, U., Haferlach, C. et al. Rare CBFB-MYH11 fusion transcripts in AML with inv(16)/t(16;16) are associated with therapy-related AML M4eo, atypical cytomorphology, atypical immunophenotype, atypical additional chromosomal rearrangements and low white blood cell count: a study on 162 patients. Leukemia 21, 725–731 (2007). https://doi.org/10.1038/sj.leu.2404531

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