{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:44:43Z","timestamp":1791305083618,"version":"4.3.1"},"reference-count":42,"publisher":"American Society of Hematology","issue":"12","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,6,15]]},"abstract":"<jats:p>Sixty-four patients with adult T-cell leukemia\/lymphoma (ATL; 18 patients with indolent subtype and 46 with aggressive subtype) associated with human T-lymphotropic virus type 1 (HTLV-1) were analyzed using comparative genomic hybridization (CGH). The most frequent observations were gains at chromosomes 14q, 7q, and 3p and losses at chromosomes 6q and 13q. Chromosome imbalances, losses, and gains were more frequently observed in aggressive ATL than in indolent ATL, with significant differences between the 2 ATL subtypes at gains of 1q and 4q. An increased number of chromosomal imbalances was associated with a significantly shorter survival in all patients. A high number of chromosomal losses was associated with a poor prognosis in indolent ATL, whereas the presence of 7q+ was marginally associated with a good prognosis in aggressive ATL. Paired samples (ie, samples obtained at different sites from 4 patients) and sequential samples from 13 patients (from 6 during both chronic disease and acute crisis and from 7 during both acute onset and relapse) were examined by CGH and Southern blotting for HTLV-1. All but 2 paired samples showed differences on CGH assessment. Two chronic\/crisis samples showed distinct results regarding both CGH and HTLV-1 integration sites, indicating clonal changes in ATL at crisis. In 11 patients, the finding of identical HTLV-1 sites and clonally related CGH results suggested a common origin of sequential samples. In contrast to chronic\/crisis samples, CGH results with all acute\/relapse sample pairs showed the presence of clonally related but not evolutional subclones at relapse, thereby suggesting marked chromosomal instability. In summary, clonal diversity is common during progression of ATL, and CGH alterations are associated with clinical course.<\/jats:p>","DOI":"10.1182\/blood.v97.12.3875","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:47Z","timestamp":1027774007000},"page":"3875-3881","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":98,"title":["Comparative genomic hybridization analysis in adult T-cell leukemia\/lymphoma: correlation with clinical course"],"prefix":"10.1182","volume":"97","author":[{"given":"Kunihiro","family":"Tsukasaki","sequence":"first","affiliation":[{"name":"From the Division of Hematology\/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA; the Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany; and the Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, Nagasaki, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Krebs","sequence":"additional","affiliation":[{"name":"From the Division of Hematology\/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA; the Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany; and the Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, Nagasaki, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Nagai","sequence":"additional","affiliation":[{"name":"From the Division of Hematology\/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA; the Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany; and the Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, Nagasaki, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Tomonaga","sequence":"additional","affiliation":[{"name":"From the Division of Hematology\/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA; the Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany; and the Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, Nagasaki, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Phillip","family":"Koeffler","sequence":"additional","affiliation":[{"name":"From the Division of Hematology\/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA; the Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany; and the Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, Nagasaki, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus R.","family":"Bartram","sequence":"additional","affiliation":[{"name":"From the Division of Hematology\/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA; the Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany; and the Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, Nagasaki, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Jauch","sequence":"additional","affiliation":[{"name":"From the Division of Hematology\/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA; the Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany; and the Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, Nagasaki, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021221223828800_B1","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1182\/blood.V50.3.481.481","article-title":"Adult T-cell leukemia: clinical and hematologic features of 16 cases.","volume":"50","author":"Uchiyama","year":"1997","journal-title":"Blood."},{"key":"2020021221223828800_B2","doi-asserted-by":"crossref","first-page":"7415","DOI":"10.1073\/pnas.77.12.7415","article-title":"Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma.","volume":"77","author":"Poiesz","year":"1980","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2020021221223828800_B3","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1111\/j.1365-2141.1991.tb08051.x","article-title":"Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma: a report from the Lymphoma Study Group (1984-87).","volume":"79","author":"Shimoyama","year":"1991","journal-title":"Br J Haematol."},{"key":"2020021221223828800_B4","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/0145-2126(91)90087-A","article-title":"Major prognostic factors of patients with adult T-cell leukemia-lymphoma: a cooperative study. Lymphoma Study Group (1984-1987).","volume":"15","year":"1991","journal-title":"Leuk Res."},{"key":"2020021221223828800_B5","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1002\/1097-0142(19910515)67:10<2605::AID-CNCR2820671034>3.0.CO;2-L","article-title":"Prognostic significance of the proportion of Ki-67-positive cells in adult T-cell leukemia.","volume":"67","author":"Yamada","year":"1991","journal-title":"Cancer."},{"key":"2020021221223828800_B6","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/0145-2126(92)90168-7","article-title":"Phenotypic diversity and prognosis of adult T-cell leukemia.","volume":"16","author":"Kamihira","year":"1992","journal-title":"Leuk Res."},{"key":"2020021221223828800_B7","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1182\/blood.V89.3.948","article-title":"Integration patterns of HTLV-I provirus in relation to the clinical course of ATL: frequent clonal change at crisis from indolent disease.","volume":"89","author":"Tsukasaki","year":"1997","journal-title":"Blood."},{"key":"2020021221223828800_B8","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1200\/JCO.1997.15.5.1778","article-title":"Deletions of p15 and\/or p16 genes as a poor-prognosis factor in adult T-cell leukemia.","volume":"15","author":"Yamada","year":"1997","journal-title":"J Clin Oncol."},{"key":"2020021221223828800_B9","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1002\/ijc.2910400605","article-title":"Epidemiological features of HTLV-I carriers and incidence of ATL in an ATL-endemic island: a report of the community-based co-operative study in Tsushima, Japan.","volume":"40","author":"Tajima","year":"1987","journal-title":"Intl J Cancer."},{"key":"2020021221223828800_B10","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/j.1349-7006.1989.tb02289.x","article-title":"Multi-step carcinogenesis model for adult T-cell leukemia.","volume":"80","author":"Okamoto","year":"1989","journal-title":"Jpn J Cancer Res."},{"key":"2020021221223828800_B11","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1182\/blood.V79.2.477.477","article-title":"Mutations of the p53 gene in adult T-cell leukemia.","volume":"79","author":"Sakashita","year":"1992","journal-title":"Blood."},{"key":"2020021221223828800_B12","first-page":"1481","article-title":"Chromosome abnormalities in adult T-cell leukemia\/lymphoma: a karyotype review committee report.","volume":"52","author":"Kamada","year":"1992","journal-title":"Cancer Res."},{"key":"2020021221223828800_B13","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1053\/beha.1999.0070","article-title":"Human T-lymphotropic virus type 1 infection.","volume":"13","author":"Tsukasaki","year":"2000","journal-title":"Baillieres Best Pract Res Clin Haematol."},{"key":"2020021221223828800_B14","first-page":"1253","article-title":"Comparative genomic hybridization: an overview.","volume":"145","author":"Houldsworth","year":"1994","journal-title":"Am J Pathol."},{"key":"2020021221223828800_B15","doi-asserted-by":"crossref","first-page":"6476","DOI":"10.1073\/pnas.78.10.6476","article-title":"Adult T-cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera.","volume":"78","author":"Hinuma","year":"1981","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2020021221223828800_B16","first-page":"185","article-title":"Enzyme-linked immunosorbent assay of antibodies to adult T-cell leukemia-associated antigens.","volume":"74","author":"Taguchi","year":"1983","journal-title":"Gann."},{"key":"2020021221223828800_B17","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1007\/BF00202476","article-title":"Detection of complete and partial chromosome gains and losses by comparative genomic in situ hybridization.","volume":"90","author":"du Manoir","year":"1993","journal-title":"Hum Genet."},{"key":"2020021221223828800_B18","first-page":"191","article-title":"Comparative genomic hybridization. In Verma R, Babu A, eds.","volume-title":"Human Chromosomes.","author":"Lichter","year":"1995"},{"key":"2020021221223828800_B19","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/0145-2126(93)90061-O","article-title":"Characteristics of chemotherapy-induced clinical remission in long survivors with aggressive adult T-cell leukemia\/lymphoma.","volume":"17","author":"Tsukasaki","year":"1993","journal-title":"Leuk Res."},{"key":"2020021221223828800_B20","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s100380050178","article-title":"Chromosomal imbalances in adult T-cell leukemia revealed by comparative genomic hybridization: gains at 14q32 and 2p16\u201322 in cell lines.","volume":"44","author":"Ariyama","year":"1999","journal-title":"J Hum Genet."},{"key":"2020021221223828800_B21","first-page":"1107","article-title":"DNA copy number amplifications in human neoplasms.","volume":"152","author":"Knuutila","year":"1998","journal-title":"Am J Pathol."},{"key":"2020021221223828800_B22","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1086\/301973","article-title":"From amplification to gene in thyroid cancer: a high-resolution mapped bacterial-artificial-chromosome resource for cancer chromosome aberrations guides gene discovery after comparative genome hybridization.","volume":"63","author":"Chen","year":"1998","journal-title":"Am J Hum Genet."},{"key":"2020021221223828800_B23","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/(SICI)1098-2264(200006)28:2<145::AID-GCC3>3.0.CO;2-7","article-title":"Adrenocortical carcinoma is characterized by a high frequency of chromosomal gains and high-level amplifications.","volume":"28","author":"Dohna","year":"2000","journal-title":"Genes Chromosomes Cancer."},{"key":"2020021221223828800_B24","doi-asserted-by":"crossref","first-page":"9275","DOI":"10.1073\/pnas.90.20.9275","article-title":"Chromosome walking on the TCL1 locus involved in T-cell neoplasia.","volume":"90","author":"Virgilio","year":"1993","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2020021221223828800_B25","first-page":"499a","article-title":"Molecular cytogenetic analysis of chromosome 14 at band q32 region in adult T-cell leukemia [abstract].","volume":"94","author":"Itoyama","year":"1999","journal-title":"Blood."},{"key":"2020021221223828800_B26","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/(SICI)1098-2264(199803)21:3<195::AID-GCC3>3.0.CO;2-V","article-title":"Genetic analysis of glioblastoma multiforme provides evidence for subgroups within the grade.","volume":"21","author":"Mohapatra","year":"1998","journal-title":"Genes Chromosomes Cancer."},{"key":"2020021221223828800_B27","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1111\/j.1349-7006.2000.tb00927.x","article-title":"Molecular cytogenetic analysis of 17 renal cancer cell lines: increased copy number at 5q31\u201333 in cell lines from nonpapillary carcinomas.","volume":"91","author":"Yang","year":"2000","journal-title":"Jpn J Cancer Res."},{"key":"2020021221223828800_B28","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/(SICI)1098-2264(199809)23:1<44::AID-GCC7>3.0.CO;2-6","article-title":"Cytogenetic and molecular characterization of random chromosomal rearrangements activating the drug resistance gene, MDR1\/P-glycoprotein, in drug-selected cell lines and patients with drug refractory ALL.","volume":"23","author":"Knutsen","year":"1998","journal-title":"Genes Chromosomes Cancer."},{"key":"2020021221223828800_B29","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/BF02905214","article-title":"Diagnostics of multidrug resistance in cancer.","volume":"4","author":"Szakacs","year":"1998","journal-title":"Pathol Oncol Res."},{"key":"2020021221223828800_B30","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1182\/blood.V76.10.2065.2065","article-title":"Expression of P-glycoprotein in adult T-cell leukemia cells.","volume":"76","author":"Kuwazuru","year":"1990","journal-title":"Blood."},{"key":"2020021221223828800_B31","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1182\/blood.V88.4.1418.bloodjournal8841418","article-title":"Localization by chromosome microdissection of a recurrent breakpoint region on chromosome 6 in human B-cell lymphoma.","volume":"88","author":"Guan","year":"1996","journal-title":"Blood."},{"key":"2020021221223828800_B32","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1002\/(SICI)1098-2264(200003)27:3<319::AID-GCC13>3.0.CO;2-P","article-title":"Molecular analysis of the candidate tumor suppressor gene ING1 in human head and neck tumors with 13q deletions.","volume":"27","author":"Sanchez-Cespedes","year":"2000","journal-title":"Genes Chromosomes Cancer."},{"key":"2020021221223828800_B33","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1046\/j.1365-2141.1998.00582.x","article-title":"Management of adult T-cell leukaemia\/lymphoma.","volume":"100","author":"Pawson","year":"1998","journal-title":"Br J Haematol."},{"key":"2020021221223828800_B34","first-page":"983","article-title":"Characterization of genomic alterations associated with glioma progression by comparative genomic hybridization.","volume":"13","author":"Weber","year":"1996","journal-title":"Oncogene."},{"key":"2020021221223828800_B35","first-page":"481","article-title":"Comparison of DNA gains and losses in primary renal clear cell carcinomas and metastatic sites: importance of 1q and 3p copy number changes in metastatic events.","volume":"57","author":"Gronwald","year":"1997","journal-title":"Cancer Res."},{"key":"2020021221223828800_B36","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/S0140-6736(84)92566-2","article-title":"Lymphoproliferative disorders in cardiac transplant recipients are multiclonal lymphomas.","volume":"2","author":"Cleary","year":"1984","journal-title":"Lancet."},{"key":"2020021221223828800_B37","first-page":"2419","article-title":"Proliferation of HTLV-1 infected circulating cells in vivo in all asymptomatic carriers and patients with TSP\/HAM.","volume":"12","author":"Cavrois","year":"1996","journal-title":"Oncogene."},{"key":"2020021221223828800_B38","first-page":"5911","article-title":"Genetic convergence and divergence in tumor progression.","volume":"48","author":"Heim","year":"1988","journal-title":"Cancer Res."},{"key":"2020021221223828800_B39","first-page":"1597","article-title":"Genetic heterogeneity and clonal evolution underlying development of asynchronous metastasis in human breast cancer.","volume":"57","author":"Kuukasjarvi","year":"1997","journal-title":"Cancer Res."},{"key":"2020021221223828800_B40","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/(SICI)1098-2264(199908)25:4<323::AID-GCC3>3.0.CO;2-5","article-title":"Comparison of genetic changes in primary sarcomas and their pulmonary metastases.","volume":"25","author":"Tarkkanen","year":"1999","journal-title":"Genes Chromosomes Cancer."},{"key":"2020021221223828800_B41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0165-4608(98)00141-1","article-title":"High rate of chromosomal abnormalities in HTLV-I-infected T-cell colonies derived from prodromal phase of adult T-cell leukemia: a study of IL-2-stimulated colony formation in methylcellulose.","volume":"109","author":"Fujimoto","year":"1999","journal-title":"Cancer Genet Cytogenet."},{"key":"2020021221223828800_B42","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1038\/25292","article-title":"Genetic instabilities in human cancers.","volume":"396","author":"Lengauer","year":"1998","journal-title":"Nature."}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/97\/12\/3875\/1675044\/h8120103875.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/97\/12\/3875\/1675044\/h8120103875.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,2,13]],"date-time":"2020-02-13T02:22:49Z","timestamp":1581560569000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/97\/12\/3875\/107221\/Comparative-genomic-hybridization-analysis-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,6,15]]},"references-count":42,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2001,6,15]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.v97.12.3875","relation":{},"ISSN":["1528-0020","0006-4971"],"issn-type":[{"value":"1528-0020","type":"electronic"},{"value":"0006-4971","type":"print"}],"subject":[],"published":{"date-parts":[[2001,6,15]]}}}