title: Molecular characterization of chronic-type adult T-cell leukemia/lymphoma.
abstract: Adult T-cell leukemia/lymphoma (ATL) is a human T-cell leukemia virus type-1-induced neoplasm with four clinical subtypes: acute, lymphoma, chronic, and smoldering. Although the chronic type is regarded as indolent ATL, about half of the cases progress to acute-type ATL. The molecular pathogenesis of acute transformation in chronic-type ATL is only partially understood. In an effort to determine the molecular pathogeneses of ATL, and especially the molecular mechanism of acute transformation, oligo-array comparative genomic hybridization and comprehensive gene expression profiling were applied to 27 and 35 cases of chronic and acute type ATL, respectively. The genomic profile of the chronic type was nearly identical to that of acute-type ATL, although more genomic alterations characteristic of acute-type ATL were observed. Among the genomic alterations frequently observed in acute-type ATL, the loss of CDKN2A, which is involved in cell-cycle deregulation, was especially characteristic of acute-type ATL compared with chronic-type ATL. Furthermore, we found that genomic alteration of CD58, which is implicated in escape from the immunosurveillance mechanism, is more frequently observed in acute-type ATL than in the chronic-type. Interestingly, the chronic-type cases with cell-cycle deregulation and disruption of immunosurveillance mechanism were associated with earlier progression to acute-type ATL. These findings suggested that cell-cycle deregulation and the immune escape mechanism play important roles in acute transformation of the chronic type and indicated that these alterations are good predictive markers for chronic-type ATL.
authors.affiliation: Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan. Department of Cancer Genetics, Nagoya University Graduate School of Medicine at Aichi Cancer Center Research Institute, Nagoya, Japan. Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Yoshida
authors.affiliation: Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: Kennosuke
authors.initials: K
authors.lastname: Karube
authors.affiliation: Department of Hematology, Imamura Bun-in Hospital, Kagoshima, Japan.
authors.forename: Atae
authors.initials: A
authors.lastname: Utsunomiya
authors.affiliation: Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Tsukasaki
authors.affiliation: Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Imaizumi
authors.affiliation: Department of Internal Medicine, Heart Life Hospital, Nakagusukuson, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Taira
authors.affiliation: Department of Hematology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Naokuni
authors.initials: N
authors.lastname: Uike
authors.affiliation: Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan. Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Umino
authors.affiliation: Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan. Third Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Arita
authors.affiliation: Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Suguro
authors.affiliation: Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Tsuzuki
authors.affiliation: Department of Hematology and Cell Therapy, Aichi Cancer Center, Nagoya, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kinoshita
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohshima
authors.affiliation: Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan. Department of Cancer Genetics, Nagoya University Graduate School of Medicine at Aichi Cancer Center Research Institute, Nagoya, Japan. Department of Pathology, Kurume University School of Medicine, Kurume, Japan. seto_masao@kurume-u.ac.jp mseto@aichi-cc.jp.
authors.forename: Masao
authors.initials: M
authors.lastname: Seto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018968:CD58 Antigens / Q000096:biosynthesis; D002453:Cell Cycle / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*
chemical_list: D018968:CD58 Antigens; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins