Advertisement

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
    Search for articles by this author
  • 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
    Search for articles by this author
  • Hassan Nayer
    Affiliations
    Department of Pathology, Inova Fairfax Hospital, Falls Church, VA, United States
    Search for articles by this author
  • Raymund S. Cuevo
    Affiliations
    Inova Schar Cancer Institute, Inova Fairfax Hospital, Falls Church, VA, United States
    Search for articles by this author
  • James B. Smadbeck
    Affiliations
    Center for Individualized Medicine-Biomarker Discovery, Mayo Clinic, Rochester, MN, United States
    Search for articles by this author
  • George Vasmatzis
    Affiliations
    Center for Individualized Medicine-Biomarker Discovery, Mayo Clinic, Rochester, MN, United States
    Search for articles by this author
  • 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
    Search for articles by this author
  • 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
    Search for articles by this author
  • 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
    Search for articles by this author
  • 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.

      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

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Cancer Genetics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      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
        • 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
        • Adams J
        • Nassiri M.
        Acute promyelocytic leukemia: a review and discussion of variant translocations.
        Arch Pathol Lab Med. 2015; 139: 1308-1313
        • 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
        • Drucker TM
        • Johnson SH
        • Murphy SJ
        • et al.
        BIMA V3: an aligner customized for mate pair library sequencing.
        Bioinformatics. 2014; 30: 1627-1629
        • 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
        • 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
        • 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
        • 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
        • 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
        • 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
        • 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
        • 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
        • 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
        • 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