Chromosome walking on the TCL1 locus involved in T-cell neoplasia.

Virgilio, Laura; Isobe, Masaharu; Narducci, Maria Grazia; Carotenuto, P; Camerini, Barbara; Kurosawa, Nobuyuki; Abbas-ar-Rushdi, [No Value]; Croce, Carlo M.; Russo, Giandomenico

doi:10.1073/pnas.90.20.9275

Cited by 71 publications

(51 citation statements)

References 28 publications

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“…T-cell leukemia gene 1 (TCL1) was identified as an oncogene overexpressed in T-cell leukemia (Virgilio et al, 1993). TCL1 transgenic mice develop B-cell malignancies such as Burkitt-like lymphoma, diffuse large B-cell lymphomas (DLBCLs), B-cell leukemias and follicular lymphomas (Bichi et al, 2002;Hoyer et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Epstein–Barr virus encoded LMP1 downregulates TCL1 oncogene through miR-29b

et al. 2009

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Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is noted for its transforming potential. Yet, it also acts as a cytostatic and growth-relenting factor in Burkitt's lymphoma (BL) cells. The underlying molecular mechanisms of the growth inhibitory property of LMP1 have remained largely unknown. In this study, we show that LMP1 negatively regulates a major oncogene, TCL1, in diffuse large B-cell lymphoma (DLBCL) and BL cells. MicroRNA (miR) profiling of LMP1 transfectants showed that among others, miR-29b, is upregulated. LMP1 diminished TCL1 by inducing miR29b through C-terminus activation region 1 (CTAR1) and CTAR2. miR-29b locked nucleic acid (LNA) antisense oligonucleotide transfection into LMP1-expressing cells reduced miR-29b expression and consequently reconstituted TCL1, suggesting that LMP1 negatively regulates TCL1 through miR-29b upregulation. The miR-29b increase by LMP1 was due to an increase in the cluster pri-miR-29b1-a transcription, derived from human chromosome 7. Using pharmacological inhibitors, we found that p38 mitogen-activated protein kinase-activating function of LMP1 is important for this effect. The ability of LMP1 to negatively regulate TCL1 through miR-29b might underlie its B-cell lymphoma growth antagonistic property. As LMP1 is also important for B-cell transformation, we suggest that the functional dichotomy of this viral protein may depend on a combination of levels of its expression, lineage and differentiation of the target cells and regulation of miRs, which then directs the outcome of the cellular response.

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Section: Introductionmentioning

confidence: 99%

Epstein–Barr virus encoded LMP1 downregulates TCL1 oncogene through miR-29b

et al. 2009

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“…To explore the mechanism responsible for the transcriptional diversity, we isolated and sequenced subclones corresponding to the entire TCL6 gene from P1 clones (P1 7-4 and P1 20-7) (Virgilio et al, 1993). The map and structure of the TCL6 gene are shown together with those of the TML1 and TCL1 genes in Figures 1 and 2.…”

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confidence: 99%

Identification of the TCL6 genes within the breakpoint cluster region on chromosome 14q32 in T-cell leukemia

et al. 2000

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A region on chromosome 14q32.1 is often involved in chromosomal translocations and inversions with one of the T-cell receptor loci in T-cell lymphoproliferative diseases. The breakpoints of the di erent rearrangements segregate into two clusters; a cluster due to inversion on the centromeric side and a cluster due to simple balanced translocations on the telomeric side. If the target gene activated by these di erent types of chromosomal rearrangements is the same, the gene must be localized between the two clusters of breakpoints in a region of around 160 kb. Within this breakpoint cluster region, we isolated two genes; namely, TCL1 and TML1/TCL1b genes. In the course of characterizing the TML1 gene, we further identi®ed a third novel gene, which we named TCL6 (T-cell leukemia/lymphoma 6), from a region 7 kb upstream of the TML1 locus. The TCL6 gene expressed at least 11 isoforms through very complex alternativesplicing, including splicing with the TML1 gene. Those isoforms encode at least ®ve open reading frames (ORFs) with no homology to known sequences. The localization of the proteins corresponding to these ORF was determined by fusing green¯uorescence protein at the carboxyl terminal of each ORF. ORF141 and ORF72 were observed in the cytoplasmic region, while ORF105, ORF119, and ORF163 were predominantly localized in the nuclear region. Since the TCL6 gene was expressed in T-cell leukemia carrying a t(14;14) (q11;q32.1) chromosome translocation and was not expressed in normal T-cells (just like the TML1 and TCL1 genes), it is also a candidate gene potentially involved in leukemogenesis.

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“…[1][2][3][4] The ensuing aberrant influence of a TCR enhancer element results in overexpression of the TCL1 or MTCP1 genes. 5,6 Overexpression of either TCL1 or MTCP1 in transgenic mouse models employing a T-cell-specific promoter may also result in a T-cell leukemia that resembles human T-PLL.…”

Section: Introductionmentioning

confidence: 99%

Impaired T- and B-cell development in Tcl1-deficient mice

Kang

Narducci

Lazzeri

et al. 2005

Blood

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IntroductionT-cell prolymphocytic leukemias (T-PLLs) in humans often have chromosomal translocations that juxtapose the T-cell receptor (TCR) ␣/␦ or ␤ locus to the proximity of the T-cell leukemia/ lymphoma-1 gene (TCL1) located in the 14q32.1 region or, less frequently, to lay near its mature T-cell proliferation 1 (MTCP1) gene homolog in the Xq23 region. [1][2][3][4] The ensuing aberrant influence of a TCR enhancer element results in overexpression of the TCL1 or MTCP1 genes. 5,6 Overexpression of either TCL1 or MTCP1 in transgenic mouse models employing a T-cell-specific promoter may also result in a T-cell leukemia that resembles human T-PLL. 7,8 In addition to the implicit TCL1 involvement in this T-cell malignancy, a variety of B-lineage tumor cell lines, ranging from pre-B cell to mature B-cell phenotype, have also been shown to express high Tcl1 levels. [9][10][11] Moreover, TCL1 overexpression under the control of B-lineage-specific enhancer and promoter elements has been shown to promote B-cell chronic lymphocytic leukemia 12 and B-cell lymphomas in mice. 13 An important clue to the role of TCL1 in the leukomogenesis process is provided by the functional linkage of Tcl1 to Akt kinase, an intracellular component that participates in the transduction of antiapoptotic and proliferative signals. 14,15 In the Akt signaling cascade, Tcl1 acts as an Akt cofactor to enhance kinase activity and nuclear translocation. 16,17 Tcl1 binding to Akt also facilitates the formation of Akt-Tcl1 hetero-oligomers. 18 The resultant (trans)phosphorylation of Akt1 at Ser473 may thus amplify the phosphatidylinositol 3 (PI3)-Akt1 pathway to contribute a survival advantage. 19 Normally, TCL1 expression is tightly regulated, being confined to lymphoid and germinal cells in humans and mice. In human B-lineage cells, TCL1 expression is initiated in pro-B cells, peaks in the pre-B cells, and persists in immunoglobulin M (IgM)-bearing B cells. 5 High expression levels of TCL1 transcripts have been found in the mantle zone B cells in the spleen, whereas TCL1 expression is down-regulated in germinal center and marginal zone B cells, and is extinguished in terminally differentiated plasma cells. [9][10][11] In human T-lineage cells, TCL1 expression is seen in the intrathymic CD4 Ϫ CD8 Ϫ subpopulation, but not in mature T cells. In the present study, we observed a similar pattern for Tcl1 expression in mouse T-and B-lineage cells. In order to gain insight into the physiologic role(s) that Tcl1 may have in T and B lymphopoiesis, we have examined both pathways of lymphocyte development and their cooperative function in antibody responses of Tcl1-deficient mice. These mice are shown to have modestly compromised T and B lymphopoiesis due either to impaired cellular proliferation or enhanced apoptosis. Materials and methodsMice, cell preparation, cell counting, and statistical analysis Tcl1 Ϫ/Ϫ and Tcl1 ϩ/Ϫ mice were generated as described previously. 20 Bone marrow (BM) cells were obtained by flushing the cavities of both femoral and tibial ...

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Chromosome walking on the TCL1 locus involved in T-cell neoplasia.

Abstract: The TCLI locus on chromosome 14 band q32

Cited by 71 publications

References 28 publications

Epstein–Barr virus encoded LMP1 downregulates TCL1 oncogene through miR-29b

Epstein–Barr virus encoded LMP1 downregulates TCL1 oncogene through miR-29b

Identification of the TCL6 genes within the breakpoint cluster region on chromosome 14q32 in T-cell leukemia

Impaired T- and B-cell development in Tcl1-deficient mice

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