title: Rearrangement of the MOZ gene in pediatric therapy-related myelodysplastic syndrome with a novel chromosomal translocation t(2;8)(p23;p11).
abstract: In this study, we examined a pediatric case of therapy-related myelodysplastic syndrome (tMDS). The symptoms developed 17 months after treatment for acute myeloblastic leukemia (AML, M2 subtype according to the French-American-British [FAB] classification) involving a chromosome abnormality at t(8;21)(q22;q22). Upon diagnosis of tMDS, spectral karyotyping analysis detected a new chromosomal translocation at t(2;8)(p23;p11.2). In addition, fluorescence in situ hybridization analysis suggested a rearrangement in the monocytic leukemia zinc finger (MOZ) gene, located in the 8p11 region of chromosome 8. However, no partner gene on 2p23 could be identified. To our knowledge, this is the first report of tMDS associated with a rearrangement of the MOZ gene. MOZ-linked fusion proteins such as MOZ-CBP (CREB binding protein), MOZ-TIF2 (transcriptional intermediary factor 2), and MOZ-p300 (adenoviral E1A-associated protein) are associated with AML chromosomal abnormalities at t(8;16)(p11;p13), inv(8)(p11q13), and t(8;22)(p11;q13), respectively, and are thought to account for leukemogenesis occurring through the aberrant regulation of histone acetylation. Through a similar mechanism, we believe that MOZ, fused to an unidentified partner gene at 2p23, may have caused an alteration in histone acetylation, resulting in the development of tMDS in this patient.
authors.affiliation: Department of Pediatrics, Kyoto Prefectural University of Medicine, 465 Kaiji-cho, Hirokoji, Kamigyo-ku, Kyoto, Japan. imamura@koto.kpu-m.ac.jp
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Imamura
authors.forename: Naoki
authors.initials: N
authors.lastname: Kakazu
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Hibi
authors.forename: Akira
authors.initials: A
authors.lastname: Morimoto
authors.forename: Yoko
authors.initials: Y
authors.lastname: Fukushima
authors.forename: Ikuko
authors.initials: I
authors.lastname: Ijuin
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hada
authors.forename: Issei
authors.initials: I
authors.lastname: Kitabayashi
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Abe
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Imashuku
mesh_terms: D000123:Acetyltransferases / Q000235:genetics*; D001854:Bone Marrow Cells / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D002675:Child, Preschool; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D015321:Gene Rearrangement / Q000235:genetics*; D051548:Histone Acetyltransferases; D006801:Humans; D007621:Karyotyping / Q000379:methods; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D008297:Male; D009190:Myelodysplastic Syndromes / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D016609:Neoplasms, Second Primary / Q000235:genetics* / Q000473:pathology; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C108712:KAT6A protein, human