Cytogenetic analysis and clinical significance in adult T-cell leukemia/lymphoma: a study of 50 cases from the human T-cell leukemia virus type-1 endemic area, Nagasaki

Itoyama, Takahiro; Chaganti, R. S. K.; Yamada, Yasuaki; Tsukasaki, Kunihiro; Atogami, Sunao; Nakamura, Hideo; Tomonaga, Masao; Ohshima, Koichi; Kikuchi, Masahiro; Sadamori, Naoki

doi:10.1182/blood.v97.11.3612

Cited by 104 publications

(75 citation statements)

References 61 publications

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“…In contrast, Bcl11b À/À mice exhibit a reduced cellularity and apoptosis of thymocytes (Wakabayashi et al, 2003b), and this apoptotic phenotype seems to contradict the fact that Bcl11b being the tumor suppressor. Genetic changes of these two genes were also found in human hematopoietic malignancies (Sun et al, 1999;Bernard et al, 2001;Itoyama et al, 2001;Yagi et al, 2002;MacLeod et al, 2003;Nagel et al, 2003;Bezrookove and van Zelderen-Bhola, 2004;Przybylski et al, 2005). Studies in other laboratories implicated several genes in the lymphoma development such as Myc, Notch1 and PTEN (Klein, 1979;Graham et al, 1985;Ellisen et al, 1991;Mao et al, 2003;Lin et al, 2006;O'Neil et al, 2006).…”

Section: Introductionmentioning

confidence: 89%

Multi-step lymphomagenesis deduced from DNA changes in thymic lymphomas and atrophic thymuses at various times after γ-irradiation

et al. 2007

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Whole-body c-irradiation to mice causes thymic atrophy where a population of precancerous cells with mutation can be found. Thus, clonal growth and DNA changes at Bcl11b, Ikaros, Pten, Notch1 and Myc were examined in not only thymic lymphomas but also in atrophic thymuses at various times after irradiation. Clonal expansion was detected from the distinct patterns of rearrangements at the TCRb receptor locus in a fraction of atrophic thymuses at as early as 30 days after irradiation. This expansion may be in part owing to the rearranged TCRb signaling because the transfer of bone marrow cells with the rearrangement and the wild-type locus into severecombined immunodeficiency mice showed preferential growth of the rearranged thymocytes in atrophic thymus. Loss of heterozygosity (LOH) at Bcl11b and trisomy of Myc were found at high frequencies in both lymphomas and atrophic thymuses, and in contrast, LOH at Ikaros and Pten were rare in atrophic thymuses but prevalent in lymphomas. Notch1 activation was detected in lymphomas and in atrophic thymuses only at a late stage. Similar patterns of DNA changes were found in atrophic thymuses induced in Bcl11b þ /À mice. These results suggest the order of genetic changes during lymphomagenesis, Bcl11b and Myc being at the early stage; whereas Ikaros, Pten and Notch1 at the late stage.

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Section: Introductionmentioning

confidence: 89%

Multi-step lymphomagenesis deduced from DNA changes in thymic lymphomas and atrophic thymuses at various times after γ-irradiation

et al. 2007

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“…Moreover, the breaks in 14q32 in ATLL seem not to target TCL1. 46 They have been reported to map mostly between TCL1 and the telomeric marker D14S250 although no candidate oncogenes in ATLL have been described so far. 47 A gene located in that region is BCL11B/CTIP2.…”

Section: Discussionmentioning

confidence: 99%

Molecular cytogenetic detection of chromosomal breakpoints in T-cell receptor gene loci

et al. 2003

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Chromosomal aberrations with breakpoints in T-cell receptor (TCR) gene loci are recurrent in several T-cell malignancies. Although the importance of interphase cytogenetics has been extensively shown in B-cell lymphomas, hardly any molecular cytogenetic tools are available for recurrent changes in T-cell disorders. Thus, we have established fluorescence in situ hybridization (FISH)-based break-apart assays for the TCRA/D (14q11), TCRB (7q34) and TCRG (7p14) genes and the TCL cluster (14q32). The assays were validated in normal controls as well as in 43 T-cell malignancies with cytogenetically proven 14q11, 7q34-35 or 7p13-21 aberrations. Breakpoints in TCRA/D, TCRB and TCRG could be diagnosed by these assays in 32/33 T-cell neoplasms with chromosome 14q11, 3/6 with 7q34-35 and 1/7 with 7p13-21 alterations, respectively. Application of the new FISH assays to a series of 24 angioimmunoblastic and 12 cutaneous T-cell lymphomas confirmed the cytogenetic evidence of lack of breakpoints in the TCRA/D or TCRB locus. Simultaneous detection of TCRA/D or TCRB breaks was achieved in a multicolor approach, which was further combined with detection of the T-cell-specific CD3 antigen in a multicolor FICTION (Fluorescence Immunophenotyping and Interphase Cytogenetics as a Tool for the Investigation of Neoplasm) assay. These new FISH and FICTION assays provide sensitive, rapid and accurate tools for the diagnosis and biological characterization of T-cell malignancies.

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“…23 In contrast, in ATLL the involvement of either IGH or TCL genes was excluded in the majority of cases with 14q32 alterations. 25 To our knowledge, hardly any molecular breakpoint analyses have been performed on T-ALL inv(14)(q11q32) or t(14;14)(q11;q32). 24 The first molecular analysis of inv(14)(q11q32) was performed in the childhood lymphoblastic T-cell lymphoma-derived cell line SUP T1 and demonstrated joining between an immunoglobulin heavy-chain variable gene segment (VH) with a Ja segment from the TCRA/D locus.…”

Section: Discussionmentioning

confidence: 99%

Disruption of the BCL11B gene through inv(14)(q11.2q32.31) results in the expression of BCL11B-TRDC fusion transcripts and is associated with the absence of wild-type BCL11B transcripts in T-ALL

et al. 2005

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T-cell acute lymphoblastic leukemia (T-ALL) is associated with chromosomal aberrations characterized by juxtaposition of proto-oncogenes to T-cell receptor gene loci (TCR), resulting in the deregulated transcription of these proto-oncogenes. Here, we describe the molecular characterization of a novel chromosomal aberration, inv(14)(q11.2q32.31), in a T-ALL sample, involving the recently described BCL11B gene and the TCRD locus. The inversion joined the 5 0 part of BCL11B, including exons 1-3, to the TRDD3 gene segment of the TCRD locus, whereas the reciprocal breakpoint fused the TRDV1 gene segment to the fourth exon of BCL11B. The TRDV1-BCL11B joining region was 1344 bp long and contained fragments derived from 20q11.22, 3p21.33 and from 11p12, indicating the complex character of this aberration. A strong expression of inframe transcripts with truncated BCL11B and TCRD constant region (TRDC) were observed, but in contrast to normal T cells and other T-ALL samples, no wild-type BCL11B transcripts were detected in the T-ALL sample. Screening of 37 other T-ALLs revealed one additional case with expression of the BCL11B-TRDC fusion transcript. As BCL11B appears to play a key role in T-cell differentiation, BCL11B disruption and disturbed expression may contribute to the development of T-cell malignancies in man.

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Cytogenetic analysis and clinical significance in adult T-cell leukemia/lymphoma: a study of 50 cases from the human T-cell leukemia virus type-1 endemic area, Nagasaki

Cited by 104 publications

References 61 publications

Multi-step lymphomagenesis deduced from DNA changes in thymic lymphomas and atrophic thymuses at various times after γ-irradiation

Multi-step lymphomagenesis deduced from DNA changes in thymic lymphomas and atrophic thymuses at various times after γ-irradiation

Molecular cytogenetic detection of chromosomal breakpoints in T-cell receptor gene loci

Disruption of the BCL11B gene through inv(14)(q11.2q32.31) results in the expression of BCL11B-TRDC fusion transcripts and is associated with the absence of wild-type BCL11B transcripts in T-ALL

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