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Cytogenetics and Molecular Genetics

AML with translocation t(8;16)(p11;p13) demonstrates unique cytomorphological, cytogenetic, molecular and prognostic features

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Abstract

Balanced chromosomal rearrangements define distinct entities in acute myeloid leukemia (AML). Here, we present 13 AML cases with t(8;16)(p11;p13) with observed low incidence (13/6124 patients), but more frequent presentation in therapy-related AML than in de novo AML (7/438 versus 6/5686, P=0.00001). Prognosis was poor with median overall survival of 4.7 months. Cytomorphology was characterized by parallel positive myeloperoxidase and non-specific esterase staining, therefore, French–American–British (FAB)-classification was impossible and origin of the AML with t(8;16) from an early stem cell with myeloid and monoblastic potential is hypothesized. Erythrophagocytosis was observed in 7/13 cases. Using gene expression profiling on 407 cases, patients with t(8;16) were compared to AML FAB subtypes with normal karyotype. Principal component analyses demonstrated that AML with t(8;16) were distinct from FAB subtypes M1, M4, M5a/b. When further compared to AML showing balanced rearrangements, that is, current WHO categories t(15;17), t(8;21), inv(16) and t(11q23)/MLL, AML with t(8;16) cases were clustered close to t(11q23)/MLL sharing commonly expressed genes. Subsequently, a pairwise comparison discriminated AML with t(8;16) from AML with t(11q23)/MLL, thus defining a highly unique signature for AML with t(8;16). In conclusion, AML with t(8;16) demonstrates unique cytomorphological, cytogenetic, molecular and prognostic features and is a specific subtype of AML.

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Acknowledgements

This study was supported in part by a grant from the German José Carreras Foundation (DJCS-R00/13). Microarray analyses were further supported in part by Roche Diagnostics GmbH, Penzberg, Germany and Roche Molecular Systems, Pleasanton, CA, USA.

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Author notes

  1. H Löffler: Dr H Löffler is a Professor Emeritus in retirement.

  2. T Haferlach and A Kohlmann: These authors contributed equally to this work.

Authors and Affiliations

  1. MLL Munich Leukemia Laboratory, Munich, Germany

    T Haferlach, A Kohlmann, W Kern, S Schnittger & C Haferlach

  2. Department of Medical Informatics and Biomathematics, University of Münster, M, ü, nster, Germany

    H-U Klein, C Ruckert & M Dugas

  3. Department of Genomics and Oncology, Roche Molecular Systems Inc., Pleasanton, CA, USA

    P M Williams

  4. Department of Stem Cell Transplantation, University Cancer Center Hamburg, Hamburg, Germany

    U Bacher

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  1. T Haferlach
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  2. A Kohlmann
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  3. H-U Klein
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Correspondence to T Haferlach.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Haferlach, T., Kohlmann, A., Klein, HU. et al. AML with translocation t(8;16)(p11;p13) demonstrates unique cytomorphological, cytogenetic, molecular and prognostic features. Leukemia 23, 934–943 (2009). https://doi.org/10.1038/leu.2008.388

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