Comparative genomic hybridization analysis in adult T-cell leukemia/lymphoma: correlation with clinical course

Blood ◽  
2001 ◽  
Vol 97 (12) ◽  
pp. 3875-3881 ◽  
Author(s):  
Kunihiro Tsukasaki ◽  
Johannes Krebs ◽  
Kazuhiro Nagai ◽  
Masao Tomonaga ◽  
H. Phillip Koeffler ◽  
...  

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.

Blood ◽  
2011 ◽  
Vol 117 (20) ◽  
pp. 5473-5478 ◽  
Author(s):  
Akira Umino ◽  
Masao Nakagawa ◽  
Atae Utsunomiya ◽  
Kunihiro Tsukasaki ◽  
Naoya Taira ◽  
...  

Abstract Adult T-cell leukemia/lymphoma (ATLL) is the neoplasm caused by human T-cell leukemia virus type 1 (HTLV-1). We performed oligo-array comparative genomic hybridization (CGH) against paired samples comprising peripheral blood (PB) and lymph node (LN) samples from 13 patients with acute ATLL. We found that the genome profiles of the PB frequently differed from those of the LN samples. The results showed that 9 of 13 cases investigated had a log2 ratio imbalance among chromosomes, and that chromosome imbalances were more frequent in LN samples. Detailed analysis revealed that the imbalances were likely caused by the presence of multiple subclones in the LN samples. Five of 13 cases showed homozygous loss regions in PB samples, which were not found in the LN samples, indicating that tumors in the PB were derived from LN subclones in most cases. Southern blot analysis of TCRγ showed that these multiple subclones originated from a common clone. We concluded that in many ATLL cases, multiple subclones in the LNs originate from a common clone, and that a selected subclone among the LN subclones appears in the PB.


1990 ◽  
Vol 14 (11-12) ◽  
pp. 1071 ◽  
Author(s):  
Fumio Kawano ◽  
Atsuko Tsukamoto ◽  
Masahiko Satoh ◽  
Isao Sanada ◽  
Tadahiro Shido ◽  
...  

2003 ◽  
Vol 83 (2) ◽  
pp. 139-140
Author(s):  
Takehiko Tsuda ◽  
Masashi Ishikawa ◽  
Tomohiro Banno ◽  
Hiroshi Fujisawa ◽  
Sumihisa Imakado ◽  
...  

1995 ◽  
Vol 93 (1) ◽  
pp. 40-45 ◽  
Author(s):  
Muneou Suzuki ◽  
Hisamitsu Uno ◽  
Akihiko Kiyomizu ◽  
Youko Kubuki ◽  
Kiyoshi Yamashita ◽  
...  

1987 ◽  
Vol 76 (12) ◽  
pp. 1876-1880
Author(s):  
Hideto NAKAO ◽  
Nobutaro BAN ◽  
Kazuo OTSUKA ◽  
Masataka MORI ◽  
Mikio KAWAMOTO ◽  
...  

Blood ◽  
2008 ◽  
Vol 112 (2) ◽  
pp. 383-393 ◽  
Author(s):  
Tomonori Hidaka ◽  
Shingo Nakahata ◽  
Kinta Hatakeyama ◽  
Makoto Hamasaki ◽  
Kiyoshi Yamashita ◽  
...  

Abstract Adult T-cell leukemia/lymphoma (ATLL) is caused by latent human T-lymphotropic virus-1 (HTLV-1) infection. To clarify the molecular mechanism underlying leukemogenesis after viral infection, we precisely mapped 605 chromosomal breakpoints in 61 ATLL cases by spectral karyotyping and identified frequent chromosomal breakpoints in 10p11, 14q11, and 14q32. Single nucleotide polymorphism (SNP) array–comparative genomic hybridization (CGH), genetic, and expression analyses of the genes mapped within a common breakpoint cluster region in 10p11.2 revealed that in ATLL cells, transcription factor 8 (TCF8) was frequently disrupted by several mechanisms, including mainly epigenetic dysregulation. TCF8 mutant mice frequently developed invasive CD4+ T-cell lymphomas in the thymus or in ascitic fluid in vivo. Down-regulation of TCF8 expression in ATLL cells in vitro was associated with resistance to transforming growth factor β1 (TGF-β1), a well-known characteristic of ATLL cells, suggesting that escape from TGF-β1–mediated growth inhibition is important in the pathogenesis of ATLL. These findings indicate that TCF8 has a tumor suppressor role in ATLL.


Skin Cancer ◽  
1991 ◽  
Vol 6 (1) ◽  
pp. 141-144 ◽  
Author(s):  
Tomohiro NISHIMURA ◽  
Koichi NAKAGAWA ◽  
Hiromi KOBAYASHI ◽  
Toshio HAMADA

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