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Prognostic gene mutations and distinct gene- and microRNA-expression signatures in acute myeloid leukemia with a sole trisomy 8

Leukemia volume 28, pages 1754–1758 (2014)Cite this article

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Trisomy 8 (+8) is the most frequent numerical chromosome aberration in acute myeloid leukemia (AML), occurring in ∼9% of adult patients.1 In one-third of such patients, +8 is the sole cytogenetic abnormality.1 These patients are mostly classified as having an intermediate prognosis.1, 2 The few available studies suggest that sole +8 AML is molecularly heterogeneous,3, 4, 5 but the clinical impact of mutations remains to be established. Moreover, although the biologic features of sole +8 AML have been investigated using genome-wide gene-6, 7 or microRNA-expression8 analyses, these studies included small numbers of patients.

We report herein the molecular and clinical characterization of 80 adults with de novo AML and sole +8 enrolled on Cancer and Leukemia Group B/Alliance clinical trials. Methodological details are described in the Supplementary Information.

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Acknowledgements

The Cancer and Leukemia Group B (CALGB) institutions, principal investigators and cytogeneticists participating in this study are provided in the Supplementary Information. The research was supported in part by National Cancer Institute, Bethesda, MD grants CA101140, CA140158, CA114725, CA129657, CA16058, CA77658, The Coleman Leukemia Research Foundation, the Deutsche Krebshilfe—Dr Mildred Scheel Foundation (to HB) and the Research Committee of the University Freiburg, Germany (to HB), the Pelotonia Fellowship Program (to A-KE), and the Conquer Cancer Foundation (to JHM). The research for CALGB 8461, 20202 and 9665 (Alliance) was supported, in part, by grants from the National Cancer Institute (CA31946) to the Alliance for Clinical Trials in Oncology (Monica M Bertagnolli, Chair) and to the Alliance Statistics and Data Center (Daniel J Sargent, CA33601). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. We thank Donna Bucci and the CALGB Leukemia Tissue Bank at The Ohio State University Comprehensive Cancer Center, Columbus, OH, for sample processing and storage services, Colin G Edwards, PhD, Lisa J Sterling and Christine Finks for data management, and Dean Margeson and Kelsi B Holland for assistance in the statistical analyses. Moreover, we thank Stephan M Tanner, PhD and Albert de la Chapelle, MD, PhD for scientific discussions.

Author information

Author notes

  1. H Becker

    Present address: 10Current address: Department of Internal Medicine I, Medical Center, University of Freiburg, Freiburg, Germany.,

  2. G Marcucci 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

    H Becker, K Maharry, K Mrózek, S Volinia, A-K Eisfeld, M D Radmacher, J Kohlschmidt, K H Metzeler, S Schwind, S P Whitman, J H Mendler, Y-Z Wu, D Nicolet, P Paschka, M A Caligiuri, G Marcucci & C D Bloomfield

  2. Alliance for Clinical Trials in Oncology Statistics and Data Center, Mayo Clinic, Rochester, MN, USA

    K Maharry & J Kohlschmidt

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

    B L Powell

  4. Department of Internal Medicine, University of Iowa, Iowa City, IA, USA

    T H Carter

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

    M Wetzler

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

    J E Kolitz

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

    A J Carroll

  8. Department of Medicine and Greenebaum Cancer Center, University of Maryland, Baltimore, MD, USA

    M R Baer

  9. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

    R M Stone

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  1. H Becker
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Corresponding authors

Correspondence to G Marcucci or C D Bloomfield.

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The authors declare no conflict of interest.

Additional information

Author contributions

HB, K Maharry, K Mrózek, SV, MDR, GM and CDB contributed to the design and analysis of this study and the writing of this manuscript, and all authors agreed on the final version; HB, A-KE, KHM, SS, SPW, JHM, Y-ZW and PP carried out laboratory-based research; K Maharry, SV, MDR, JK and DN performed statistical analyses; and BLP, THC, MW, JEK, AJC, MRB, MAC, RMS, GM and CDB were involved directly or indirectly in the care of patients and/or sample procurement.

Supplementary Information accompanies this paper on the Leukemia website

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Becker, H., Maharry, K., Mrózek, K. et al. Prognostic gene mutations and distinct gene- and microRNA-expression signatures in acute myeloid leukemia with a sole trisomy 8. Leukemia 28, 1754–1758 (2014). https://doi.org/10.1038/leu.2014.114

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