Down-regulation of TCF8 is involved in the leukemogenesis of adult T-cell leukemia/lymphoma

Blood ◽  
2008 ◽  
Vol 112 (2) ◽  
pp. 383-393 ◽  
Author(s):  
Tomonori Hidaka ◽  
Shingo Nakahata ◽  
Kinta Hatakeyama ◽  
Makoto Hamasaki ◽  
Kiyoshi Yamashita ◽  
...  
Keyword(s):  
T Cell ◽  
Transforming Growth Factor ◽  
Snp Array ◽  
Comparative Genomic ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Down Regulation ◽  
Adult T Cell Leukemia ◽  
Chromosomal Breakpoints ◽  
Tgf Β1

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.

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 ◽  
...  
Keyword(s):  
T Cell ◽  
Comparative Genomic Hybridization ◽  
Clinical Course ◽  
Comparative Genomic ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Genomic Hybridization ◽  
Adult T Cell Leukemia ◽  
Paired Samples ◽  
Sequential Samples

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.

Down-regulation ofASY/Nogo transcription associated with progression of adult T-cell leukemia/lymphoma

2006 ◽  
Vol 119 (7) ◽  
pp. 1648-1653 ◽  
Author(s):  
Misuzu Shimakage ◽  
Nobumasa Inoue ◽  
Kohichi Ohshima ◽  
Kunimitsu Kawahara ◽  
Takashi Oka ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Down Regulation ◽  
Adult T Cell Leukemia

Clonal evolution of adult T-cell leukemia/lymphoma takes place in the lymph nodes

Blood ◽  
2011 ◽  
Vol 117 (20) ◽  
pp. 5473-5478 ◽  
Author(s):  
Akira Umino ◽  
Masao Nakagawa ◽  
Atae Utsunomiya ◽  
Kunihiro Tsukasaki ◽  
Naoya Taira ◽  
...  
Keyword(s):  
T Cell ◽  
Clonal Evolution ◽  
Leukemia Virus ◽  
Comparative Genomic ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Adult T Cell Leukemia ◽  
Paired Samples ◽  
Human T Cell

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.

scholarly journals RNF8 Dysregulation and Down-regulation During HTLV-1 Infection Promote Genomic Instability in Adult T-Cell Leukemia

2020 ◽  
Vol 16 (5) ◽  
pp. e1008618 ◽  
Author(s):  
Huijun Zhi ◽  
Xin Guo ◽  
Yik-Khuan Ho ◽  
Nagesh Pasupala ◽  
Hampus Alexander Anders Engstrom ◽  
...  
Keyword(s):  
T Cell ◽  
Genomic Instability ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Down Regulation ◽  
Adult T Cell Leukemia

scholarly journals Failure of regulation of Tac antigen/TCGF receptor on adult T-cell leukemia cells by anti-Tac monoclonal antibody

Blood ◽  
1983 ◽  
Vol 61 (5) ◽  
pp. 1014-1016
Author(s):  
M Tsudo ◽  
T Uchiyama ◽  
H Uchino ◽  
J Yodoi
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
T Cell ◽  
Cell Lines ◽  
Leukemic Cells ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Down Regulation ◽  
Adult T Cell Leukemia ◽  
T Cell Lines

Anti-Tac monoclonal antibody, which blocks the membrane binding and action of human T-cell growth factor (TCGF), is strongly proposed to recognize TCGF receptor. We have demonstrated that anti-Tac antibody reacted with leukemic cells from patients with adult T-cell leukemia (ATL) and reacted with T-cell lines established from ATL cells. Although antigenic modulation, or down-regulation, of Tac antigen on activated normal T cells was induced by anti-Tac antibody, the expression of Tac antigen on ATL cells or T-cell lines was not affected when examined by the fluorescence-activated cell sorter (FACS) and the radioassay using 125I-staphylococcal protein A. These results indicate that regulation of Tac antigen-TCGF receptor is different between normal and malignant T cells, suggesting that failure of down- regulation of Tac antigen on leukemic cells by anti-Tac antibody may play an important role in the malignant proliferation of ATL cells.

Prognostic impact of microRNA-145 down-regulation in adult T-cell leukemia/lymphoma

2014 ◽  
Vol 45 (6) ◽  
pp. 1192-1198 ◽  
Author(s):  
Hongjing Xia ◽  
Seiji Yamada ◽  
Mineyoshi Aoyama ◽  
Fumihiko Sato ◽  
Ayako Masaki ◽  
...  
Keyword(s):  
T Cell ◽  
Prognostic Impact ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Down Regulation ◽  
Adult T Cell Leukemia
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