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Clinical features and gene- and microRNA-expression patterns in adult acute leukemia patients with t(11;19)(q23;p13.1) and t(11;19)(q23;p13.3)

Leukemia volume 30, pages 1586–1589 (2016)Cite this article

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Translocations involving the KMT2A (MLL) gene, located at 11q23, and two different partner genes, ELL and MLLT1, located at 19p13.1 and 19p13.3, respectively, have been reported in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).1, 2 However, there are limited data describing clinical and molecular differences between adult patients with t(11;19)(q23;p13.1) and those with t(11;19)(q23;p13.3). Neither the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer3 nor large studies correlating chromosome abnormalities with clinical outcome4 distinguish the two types of t(11;19); instead they combine both into one cytogenetic group. Herein, we report the largest, to our knowledge, series of 35 adults with acute leukemia and t(11;19)(q23;p13.1) or t(11;19)(q23;p13.3) who were treated on Cancer and Leukemia Group B (CALGB)/Alliance for Clinical Trials in Oncology (Alliance) trials. Our study is also the largest to describe the clinical features and disease outcomes of these patients as well as to provide mutational analyses, and gene- and microRNA (miR)-expression patterns, thereby providing the rationale to identify each as separate entities.

We identified and clinically characterized 19 adults with t(11;19)(q23;p13.1) and AML and 16 with t(11;19)(q23;p13.3), 12 with AML, three with ALL and one with ambiguous lineage acute leukemia (ALAL), who received AML-directed therapy and is grouped with AML patients, enrolled onto a prospective cytogenetics companion trial, CALGB 8461. We also performed RNA, microRNA and targeted DNA-sequencing studies on subsets of patients in each cytogenetic group. See Supplementary Information for methods details.

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Acknowledgements

Research reported in this publication was supported in part by the National Cancer Institute of the National Institutes of Health under Award Numbers U10CA180821 and U10CA180882 (to the Alliance for Clinical Trials in Oncology), U10CA180861, U10CA180850, U24CA114725, CA140158, CA16058, the Coleman Leukemia Research Foundation, the Pelotonia Fellowship Program (A-KE), the NCCN Foundation (JSB) and by an allocation of computing resources from The Ohio Supercomputer Center. The content, opinions, findings and conclusions are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health, the National Comprehensive Cancer Network (NCCN) or the NCCN Foundation.

Author contributions

BB, JSB, JK, A-KE, SV, KM, JCB and CDB contributed to the design and analysis of the study and the writing of the manuscript; A-KE performed laboratory-based research; JSB, JK, SV and DN performed statistical analyses; AJC, AWB, JEK, 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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Author notes

  1. B Bhatnagar and J S Blachly: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Hematology, Department of Internal Medicine, Columbus, OH, USA

    B Bhatnagar, J S Blachly, J C Byrd & C D Bloomfield

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

    B Bhatnagar, J S Blachly, J Kohlschmidt, A-K Eisfeld, D Nicolet, K Mrózek, J C Byrd & C D Bloomfield

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

    J Kohlschmidt & D Nicolet

  4. Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy

    S Volinia

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

    A J Carroll

  6. Roswell Park Cancer Institute, Buffalo, NY, USA

    A W Block

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

    J E Kolitz

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

    R M Stone

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  1. B Bhatnagar
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Corresponding authors

Correspondence to B Bhatnagar or C D Bloomfield.

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Supplementary Information accompanies this paper on the Leukemia website

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Bhatnagar, B., Blachly, J., Kohlschmidt, J. et al. Clinical features and gene- and microRNA-expression patterns in adult acute leukemia patients with t(11;19)(q23;p13.1) and t(11;19)(q23;p13.3). Leukemia 30, 1586–1589 (2016). https://doi.org/10.1038/leu.2015.345

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