title: RANBP2-ALK fusion combined with monosomy 7 in acute myelomonocytic leukemia.
abstract: Anaplastic lymphoma receptor tyrosine kinase (ALK) is located on chromosome 2p23; the chromosomal rearrangements of this gene are common genetic alterations, resulting in the creation of multiple fusion genes involved in tumorigenesis. However, the presence of an ALK fusion in myeloid malignancies is extremely rare. We report a case of acute myelomonocytic leukemia in a 31-year-old woman with an unusual rearrangement between RAN-binding protein 2 (RANBP2) and ALK and a karyotype of 45,XX,inv(2)(p23q21),-7[20]. We detected an ALK rearrangement using fluorescence in situ hybridization, identified the ALK fusion partner by using RNA transcriptome sequencing, and demonstrated the RANBP2-ALK fusion transcript by reverse transcriptase--PCR and Sanger sequencing. Immunohistochemistry for ALK showed strong staining of the nuclear membrane in leukemic cells. The patient had an unfavorable clinical course. Our results, together with a literature review, suggest the RANBP2-ALK fusion combined with monosomy 7 may be related to a unique clonal hematologic disorder of childhood and adolescence, characterized by myelomonocytic leukemia and a poor prognosis.
authors.affiliation: Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.
authors.forename: Ji-Hun
authors.initials: JH
authors.lastname: Lim
authors.affiliation: Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.
authors.forename: Seongsoo
authors.initials: S
authors.lastname: Jang
authors.affiliation: Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.
authors.forename: Chan-Jeoung
authors.initials: CJ
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.
authors.forename: Young-Uk
authors.initials: YU
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.
authors.forename: Je-Hwan
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.
authors.forename: Kyoo-Hyung
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea.
authors.forename: Jin-Ok
authors.initials: JO
authors.lastname: Lee
authors.affiliation: Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Korea.
authors.forename: Jong-Yeon
authors.initials: JY
authors.lastname: Shin
authors.affiliation: Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Korea.
authors.forename: Jong-Il
authors.initials: JI
authors.lastname: Kim
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.
authors.forename: Jooryung
authors.initials: J
authors.lastname: Huh
authors.affiliation: Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea. Electronic address: ejseo@amc.seoul.kr.
authors.forename: Eul-Ju
authors.initials: EJ
authors.lastname: Seo
mesh_terms: D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D001854:Bone Marrow Cells / Q000166:cytology; D007446:Chromosome Inversion; D002897:Chromosomes, Human, Pair 7; D017809:Fatal Outcome; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics* / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009006:Monosomy; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018832:Molecular Chaperones; D028861:Nuclear Pore Complex Proteins; D015514:Oncogene Proteins, Fusion; C094493:ran-binding protein 2; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: ALK; RANBP2; acute myelomonocytic leukemia; fusion gene; monosomy 7