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Adult acute myeloid leukemia with trisomy 11 as the sole abnormality is characterized by the presence of five distinct gene mutations: MLL-PTD, DNMT3A, U2AF1, FLT3-ITD and IDH2

Leukemia volume 30, pages 2254–2258 (2016)Cite this article

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Trisomy of chromosome 11 (+11) is the second most common isolated trisomy in acute myeloid leukemia (AML) patients.1 The presence of +11 is associated with intermediate2, 3 or poor patient outcomes.4, 5, 6 Whereas the clinical characteristics of solitary +11 have been well established,4, 5, 6 relatively little is known about the mutational landscape of sole +11 AML in the age of next-generation sequencing techniques that allow examination of multiple genes relevant to AML pathogenesis.6 So far, the most common molecular feature in AML with isolated +11 is the presence of a partial tandem duplication of the MLL (KMT2A) gene (MLL-PTD), which is detectable in up to 90% of patients.7 Furthermore, a frequent co-occurrence of the FLT3 internal tandem duplication (FLT3-ITD) with MLL-PTD has been reported.8 The aim of our study was to better characterize the mutational landscape of adult AML patients with sole +11.

Bone marrow (BM) or blood samples containing ⩾20% leukemic blasts were obtained from 23 AML patients with isolated +11 identified from among 1625 adult AML patients with diagnostic material available for molecular studies. Thus, the frequency of sole +11 in our AML patient cohort was 1.4%. Pretreatment cytogenetic analyses of BM and/or blood samples were performed by Cancer and Leukemia Group B (CALGB)/Alliance for Clinical Trials in Oncology (Alliance)-approved institutional laboratories and the results centrally reviewed. Trisomy 11 (found in ⩾2 metaphase cells; Supplementary Table S1) was the only clonal chromosome abnormality detected in each patient in pretreatment specimens subjected to unstimulated 24- and/or 48-h culture. The patients were treated on CALGB/Alliance trials (for details, see Supplementary Information). Study protocols were in accordance with the Declaration of Helsinki and approved by the institutional review boards at each center, and all patients provided written informed consent.

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Acknowledgements

The authors 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, for sample processing and storage services; and to Lisa J. Sterling and Chris Finks for data management. This work was supported in part by the National Cancer Institute (grants CA180821 and CA180882 (to the Alliance for Clinical Trials in Oncology), CA140158, CA180861, CA196171, CA180850, CA16058 and CA77658), the Coleman Leukemia Research Foundation, the Warren D. Brown Foundation, the Pelotonia Fellowship Program (A-KE), and by an allocation of computing resources from The Ohio Supercomputer Center.

Author contributions

A-KE, JK, KM, JCB, and CDB contributed to the study design; A-KE, JK, KM, AdlC and CDB contributed to the data interpretation, A-KE, JK, KM and CDB wrote the manuscript; A-KE and SO performed laboratory-based research; JSB and KK performed the data processing; JK and DN performed statistical analysis; AJC, RMS, KM 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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Authors and Affiliations

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

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

  2. Alliance for Clinical Trials in Oncology 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

    J S Blachly, K Kroll & J C Byrd

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

    A J Carroll

  5. Dana-Farber Cancer Institute, Boston, MA, USA

    R M Stone

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  1. A-K Eisfeld
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  10. A de la Chapelle
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Corresponding authors

Correspondence to A-K Eisfeld or C D Bloomfield.

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The authors declare no conflict of interest.

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Supplementary Information accompanies this paper on the Leukemia website

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Eisfeld, AK., Kohlschmidt, J., Mrózek, K. et al. Adult acute myeloid leukemia with trisomy 11 as the sole abnormality is characterized by the presence of five distinct gene mutations: MLL-PTD, DNMT3A, U2AF1, FLT3-ITD and IDH2. Leukemia 30, 2254–2258 (2016). https://doi.org/10.1038/leu.2016.196

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