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Case Report| Volume 237, P51-54, September 01, 2019

Characterization of a rarely reported STAT5B/RARA gene fusion in a young adult with newly diagnosed acute promyelocytic leukemia with resistance to ATRA therapy

  • Author Footnotes
    1 Both the authors contributed equally to this work.
    Jess F. Peterson
    Correspondence
    Corresponding author.
    Footnotes
    1 Both the authors contributed equally to this work.
    Affiliations
    Division of Laboratory Medicine and Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN, United States
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  • Author Footnotes
    1 Both the authors contributed equally to this work.
    Rui R. He
    Footnotes
    1 Both the authors contributed equally to this work.
    Affiliations
    Department of Pathology, Inova Fairfax Hospital, Falls Church, VA, United States
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  • Hassan Nayer
    Affiliations
    Department of Pathology, Inova Fairfax Hospital, Falls Church, VA, United States
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  • Raymund S. Cuevo
    Affiliations
    Inova Schar Cancer Institute, Inova Fairfax Hospital, Falls Church, VA, United States
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  • James B. Smadbeck
    Affiliations
    Center for Individualized Medicine-Biomarker Discovery, Mayo Clinic, Rochester, MN, United States
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  • George Vasmatzis
    Affiliations
    Center for Individualized Medicine-Biomarker Discovery, Mayo Clinic, Rochester, MN, United States
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  • Patricia T. Greipp
    Affiliations
    Division of Laboratory Medicine and Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN, United States
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  • Rhett P. Ketterling
    Affiliations
    Division of Laboratory Medicine and Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN, United States
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  • Author Footnotes
    2 Both the authors contributed equally to this work.
    Nicole L. Hoppman
    Footnotes
    2 Both the authors contributed equally to this work.
    Affiliations
    Division of Laboratory Medicine and Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN, United States
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  • Author Footnotes
    2 Both the authors contributed equally to this work.
    Linda B. Baughn
    Footnotes
    2 Both the authors contributed equally to this work.
    Affiliations
    Division of Laboratory Medicine and Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN, United States
    Search for articles by this author
  • Author Footnotes
    1 Both the authors contributed equally to this work.
    2 Both the authors contributed equally to this work.
Published:June 12, 2019DOI:https://doi.org/10.1016/j.cancergen.2019.06.007
Characterization of a rarely reported STAT5B/RARA gene fusion in a young adult with newly diagnosed acute promyelocytic leukemia with resistance to ATRA therapy
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      Highlights

      • •
        Some variant RARA rearrangements are insensitive to all-trans retinoic acid (ATRA) therapy.
      • •
        We report a rarely described STAT5B/RARA fusion that was insensitive to ATRA therapy.

      Abstract

      The detection of PML/RARA or variant RARA rearrangements is critical for the diagnosis and treatment of patients with newly diagnosed acute promyelocytic leukemia (APL). While most cases of APL harboring the PML/RARA fusion respond to all-trans retinoic acid (ATRA), some variant RARA rearrangements are ATRA insensitive. Herein, we report a 27-year-old male with newly diagnosed, rapidly progressive APL and a rarely described STAT5B/RARA fusion with known resistance to ATRA therapy. While the PML/RARA dual-color dual-fusion fluorescence in situ hybridization (FISH) probe study was negative, the RARA break-apart probe study revealed an atypical RARA rearrangement in 95% of nuclei. A next generation sequencing assay, mate-pair sequencing, was subsequently performed to further characterize the RARA rearrangement and identified the RARA gene fusion partner STAT5B.

      Keywords

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      References

        • Arber DA
        • Brunning RD
        • Le Beau MM
        • Falini B
        • Vardiman JW
        • Porwit A
        • Thiele J
        • Foucar K
        • Dohner H
        • Bloomfield CD
        • et al.
        Acute myeloid leukaemia with recurrent genetic abnormalities.
        in: Swerdlow S.H. Campo E. Harris N.L. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. International Agency for Research on Cancer (IARC), Lyon, France2017: 130-149
        View in Article
        • Melnick A
        • Licht JD.
        Deconstructing a disease: RARalpha, its fusion partners, and their roles in the pathogenesis of acute promyelocytic leukemia.
        Blood. 1999; 93: 3167-3215
        View in Article
        • Adams J
        • Nassiri M.
        Acute promyelocytic leukemia: a review and discussion of variant translocations.
        Arch Pathol Lab Med. 2015; 139: 1308-1313
        View in Article
        • Singh MK
        • Parihar M
        • Arora N
        • et al.
        Diagnosis of variant RARA translocation using standard dual-color dual-fusion PML/RARA FISH probes: an illustrative report.
        Hematol Oncol Stem Cell Ther. 2019; 12: 50-53
        View in Article
        • Drucker TM
        • Johnson SH
        • Murphy SJ
        • et al.
        BIMA V3: an aligner customized for mate pair library sequencing.
        Bioinformatics. 2014; 30: 1627-1629
        View in Article
        • Johnson SH
        • Smadbeck JB
        • Smoley SA
        • et al.
        SVAtools for junction detection of genome-wide chromosomal rearrangements by mate-pair sequencing (MPseq).
        Cancer Genet. 2018; 221: 1-18
        View in Article
        • Aypar U
        • Smoley SA
        • Pitel BA
        • et al.
        Mate pair sequencing improves detection of genomic abnormalities in acute myeloid leukemia.
        Eur J Haematol. 2019; 102: 87-96
        View in Article
        • Jovanovic JV
        • Rennie K
        • Culligan D
        • et al.
        Development of real-time quantitative polymerase chain reaction assays to track treatment response in retinoid resistant acute promyelocytic leukemia.
        Front Oncol. 2011; 1: 35
        View in Article
        • Strehl S
        • Konig M
        • Boztug
        • et al.
        All-trans retinoic acid and arsenic trioxide resistance of acute promyelocytic leukemia with the variant STAT5B-RARA fusion gene.
        Leukemia. 2013; 27: 1606-1610
        View in Article
        • Kluk MJ
        • Abo RP
        • Brown RD
        • et al.
        Myeloid neoplasm demonstrating a STAT5B-RARA rearrangement and genetic alterations associated with all-trans retinoic acid resistance by a custom next-generation sequencing assay.
        Cold Spring Harb Mol Case Stud. 2015; 1a000307
        View in Article
        • Zhang C
        • Wang Y
        • Liu B
        • et al.
        Clinical characteristics of acute promyelocytic leukemia with the STAT5B/RARA fusion gene.
        Blood Cells Mol Dis. 2018; 69: 71-73
        View in Article
        • Ciangola G
        • Gurnari C
        • Paterno G
        • et al.
        STAT5b-RARa-positive acute myeloid leukemia: diagnostic and therapeutic challenges of a rare AML subtype.
        Leuk Res. 2019; 78: 21-23
        View in Article
        • Wang A
        • Cai X
        • Qiang P
        • et al.
        Successful treatment of a patient with acute promyelocytic leukemia with a STAT5B/RARA fusion gene using decitabine.
        Leuk lymphoma. 2018; 59: 763-765
        View in Article
        • Chen H
        • Pan J
        • Yao L
        • et al.
        Acute promyelocytic leukemia with a STAT5B-RARα fusion transcript defined by arrary-CGH, FISH, and RT-PCR.
        Cancer Genet. 2012; 205: 327-331
        View in Article
        • Tomita A
        • Kiyoi H
        • Naoe T
        Mechanisms of action and resistance to all-trans- retinoic acid (ATRA) and arsenic trioxide (As2O 3) in acute promyelocytic leukemia.
        Int J Hematol. 2013; : 717-725
        View in Article

      Article Info

      Publication History

      Published online: June 12, 2019
      Accepted: June 11, 2019
      Received in revised form: June 8, 2019
      Received: May 1, 2019

      Identification

      DOI: https://doi.org/10.1016/j.cancergen.2019.06.007

      Copyright

      © 2019 Elsevier Inc. All rights reserved.

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