title: A genomic analysis of adult T-cell leukemia.
abstract: Adult T-cell leukemia (ATL) is an intractable malignancy of CD4+ T cells that is etiologically associated with infection by human T-cell leukemia virus-type I. Most individuals in the chronic stage of ATL eventually undergo progression to a highly aggressive acute stage. To clarify the mechanism responsible for this stage progression, we isolated CD4+ cells from individuals in the chronic (n=19) or acute (n=22) stages of ATL and subjected them to profiling of gene expression with DNA microarrays containing >44,000 probe sets. Changes in chromosome copy number were also examined for 24 cell specimens with the use of microarrays harboring approximately 50,000 probe sets. Stage-dependent changes in gene expression profile and chromosome copy number were apparent. Furthermore, expression of the gene for MET, a receptor tyrosine kinase for hepatocyte growth factor (HGF), was shown to be specific to the acute stage of ATL, and the plasma concentration of HGF was increased in individuals in either the acute or chronic stage. HGF induced proliferation of a MET-positive ATL cell line, and this effect was blocked by antibodies to HGF. The HGF-MET signaling pathway is thus a potential therapeutic target for ATL.
authors.affiliation: Division of Functional Genomics, Jichi Medical University, Shimotsukeshi, Tochigi, Japan.
authors.forename: Y L
authors.initials: YL
authors.lastname: Choi
authors.forename: K
authors.initials: K
authors.lastname: Tsukasaki
authors.forename: M C
authors.initials: MC
authors.lastname: O'Neill
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.forename: Y
authors.initials: Y
authors.lastname: Onimaru
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: J
authors.initials: J
authors.lastname: Ohashi
authors.forename: Y
authors.initials: Y
authors.lastname: Yamashita
authors.forename: S
authors.initials: S
authors.lastname: Tsutsumi
authors.forename: R
authors.initials: R
authors.lastname: Kaneda
authors.forename: S
authors.initials: S
authors.lastname: Takada
authors.forename: H
authors.initials: H
authors.lastname: Aburatani
authors.forename: S
authors.initials: S
authors.lastname: Kamihira
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: M
authors.initials: M
authors.lastname: Tomonaga
authors.forename: H
authors.initials: H
authors.lastname: Mano
mesh_terms: D045744:Cell Line, Tumor; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015894:Genome, Human / Q000235:genetics*; D023281:Genomics; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019859:Proto-Oncogene Proteins c-met; D017978:Receptors, Growth Factor / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met