title: Identification of a novel fusion gene, IRF2BP2-RARA, in acute promyelocytic leukemia.
abstract: Acute promyelocytic leukemia (APL) is characterized by the fusion of retinoic acid receptor alpha (RARA) with promyelocytic leukemia (PML) or, rarely, other gene partners. This report presents a patient with APL with a novel fusion between RARA and the interferon regulatory factor 2 binding protein 2 (IRF2BP2) genes. A bone marrow examination in a 19-year-old woman who presented with ecchymoses and epistaxis showed morphologic and immunophenotypic features consistent with APL. PML oncogenic domain antibody was positive. Results of fluorescence in situ hybridization, conventional cytogenetics, reverse transcription-polymerase chain reaction (RT-PCR), and oligonucleotide microarray for PML-RARA and common APL variant translocations were negative. Next-generation RNA-sequencing analysis followed by RT-PCR and direct sequencing revealed distinct breakpoints within IRF2BP2 exon 2 and RARA intron 2. The patient received all-trans retinoic acid, arsenic, and gemtuzumab ozogamicin, and achieved complete remission. However, the disease relapsed 10 months later, 2 months after consolidation therapy. This is the first report showing involvement of IRF2BP2 in APL, and it expands the list of novel RARA partners identified in APL.
authors.affiliation: From the Departments of Hematopathology, Leukemia, Genomic Medicine, and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: C Cameron
authors.initials: CC
authors.lastname: Yin
authors.affiliation: From the Departments of Hematopathology, Leukemia, Genomic Medicine, and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Nitin
authors.initials: N
authors.lastname: Jain
authors.affiliation: From the Departments of Hematopathology, Leukemia, Genomic Medicine, and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Mehrotra
authors.affiliation: From the Departments of Hematopathology, Leukemia, Genomic Medicine, and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhagn
authors.affiliation: From the Departments of Hematopathology, Leukemia, Genomic Medicine, and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Alexei
authors.initials: A
authors.lastname: Protopopov
authors.affiliation: From the Departments of Hematopathology, Leukemia, Genomic Medicine, and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Zuo
authors.affiliation: From the Departments of Hematopathology, Leukemia, Genomic Medicine, and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Naveen
authors.initials: N
authors.lastname: Pemmaraju
authors.affiliation: From the Departments of Hematopathology, Leukemia, Genomic Medicine, and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Courtney
authors.initials: C
authors.lastname: DiNardo
authors.affiliation: From the Departments of Hematopathology, Leukemia, Genomic Medicine, and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Hirsch-Ginsberg
authors.affiliation: From the Departments of Hematopathology, Leukemia, Genomic Medicine, and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sa A
authors.initials: SA
authors.lastname: Wang
authors.affiliation: From the Departments of Hematopathology, Leukemia, Genomic Medicine, and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.affiliation: From the Departments of Hematopathology, Leukemia, Genomic Medicine, and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Lynda
authors.initials: L
authors.lastname: Chin
authors.affiliation: From the Departments of Hematopathology, Leukemia, Genomic Medicine, and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Keyur P
authors.initials: KP
authors.lastname: Patel
authors.affiliation: From the Departments of Hematopathology, Leukemia, Genomic Medicine, and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.affiliation: From the Departments of Hematopathology, Leukemia, Genomic Medicine, and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Andrew
authors.initials: A
authors.lastname: Futreal
authors.affiliation: From the Departments of Hematopathology, Leukemia, Genomic Medicine, and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Bueso-Ramos
mesh_terms: D001853:Bone Marrow / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1; D002886:Chromosomes, Human, Pair 17; D004268:DNA-Binding Proteins; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000175:diagnosis* / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C475082:IRF2BP2 protein, human; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors