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Cytogenetics and molecular genetics

The mutational oncoprint of recurrent cytogenetic abnormalities in adult patients with de novo acute myeloid leukemia

Leukemia volume 31, pages 2211–2218 (2017)Cite this article

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Abstract

Recurrent chromosomal abnormalities and gene mutations detected at the time of diagnosis of acute myeloid leukemia (AML) are associated with particular disease features, treatment response and survival of AML patients, and are used to denote specific disease entities in the World Health Organization classification of myeloid neoplasms and acute leukemia. However, large studies that integrate cytogenetic and comprehensive mutational information are scarce. We created a comprehensive oncoprint of mutations associated with recurrent cytogenetic findings by combining the information on mutational patterns of 80 cancer- and leukemia-associated genes with cytogenetic findings in 1603 adult patients with de novo AML. We show unique differences in the mutational profiles among major cytogenetic subsets, identify novel associations between recurrent cytogenetic abnormalities and both specific gene mutations and gene functional groups, and reveal differences in cytogenetic and mutational features between patients younger than 60 years and those aged 60 years or older. The identified associations between cytogenetic and molecular genetic data may help guide mutation testing in AML, and result in more focused application of targeted therapy in patients with de novo AML.

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Acknowledgements

We are grateful to the patients who consented to participate in these clinical trials and the families who supported them; to Donna Bucci and the CALGB/Alliance Leukemia Tissue Bank at The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA for sample processing and storage services and Lisa J. Sterling and Christine Finks for data management. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Numbers U10CA031946, U10CA033601, U10CA180821 and U10CA180882 (to the Alliance for Clinical Trials in Oncology), U10CA101140, U10CA180850, U10CA180866, U10CA18086, U10CA032291, U10CA035279, U10CA047545, U10CA059518, CA077658, CA016058, CA140158, CA180821, CA180882, CA196171, R35 CA197734 and 5P30 CA016058; the Coleman Leukemia Research Foundation; The D Warren Brown Foundation, the Pelotonia Fellowship Program (A-KE); and by an allocation of computing resources from The Ohio Supercomputer Center.

Author contributions

A-KE, KM, JCB and CDB contributed to the study design; A-KE, KM, AdlC, JCB and CDB contributed to the data interpretation, A-KE, KM, JK, JCB and CDB wrote the manuscript; A-KE and SO performed laboratory-based research; JSB and KWK performed the data processing; JK and DN performed statistical analysis; RMS, AJC, KM, JEK, BLP, ESW and CDB were involved directly or indirectly in the care of patients and/or sample procurement. All authors read and agreed on the final version of the manuscript.

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The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Author notes

  1. A-K Eisfeld and K Mrózek: These authors contributed equally to this work.

  2. J C Byrd and C D Bloomfield: These senior authors contributed equally to this work.

Authors and Affiliations

  1. The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA

    A-K Eisfeld, K Mrózek, J Kohlschmidt, D Nicolet, C J Walker, A de la Chapelle & C D Bloomfield

  2. Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, USA

    J Kohlschmidt & D Nicolet

  3. Division of Hematology, Department of Internal Medicine, The Ohio State University, Comprehensive Cancer Center, Columbus, OH, USA

    S Orwick, K W Kroll, J S Blachly & J C Byrd

  4. Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA

    A J Carroll

  5. Monter Cancer Center, Hofstra North Shore-Long Island Jewish School of Medicine, Lake Success, NY, USA

    J E Kolitz

  6. Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC, USA

    B L Powell

  7. Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA

    E S Wang

  8. Department of Medical Oncology, Dana-Farber/Partners CancerCare, Boston, MA, USA

    R M Stone

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  1. A-K Eisfeld
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Correspondence to A-K Eisfeld, K Mrózek or C D Bloomfield.

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Eisfeld, AK., Mrózek, K., Kohlschmidt, J. et al. The mutational oncoprint of recurrent cytogenetic abnormalities in adult patients with de novo acute myeloid leukemia. Leukemia 31, 2211–2218 (2017). https://doi.org/10.1038/leu.2017.86

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