Genomic analysis of human and mouse
            <i>TCL1</i>
            loci reveals a complex of tightly clustered genes

Hallas, Cora; Pekarsky, Yuri; Itoyama, Takahiro; Varnum, James M.; Bichi, Roberta; Rothstein, Jay L.; Croce, Carlo M.

doi:10.1073/pnas.96.25.14418

Cited by 55 publications

(57 citation statements)

References 12 publications

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“…Note added in proof After we submitted the present manuscript, Hallas et al (1999) reported identifying TNG1 and TNG2 genes from the same region as that described here. Although those authors considered TNG1 and TNG2 to be independent genes, our results clearly indicate that TNG1 and TNG2 are isoforms of the TCL6 gene (corresponding to A1 and A3 type transcripts of the TCL6 gene, respectively).…”

mentioning

confidence: 84%

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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confidence: 84%

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

et al. 2000

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“…This could reflect the relatively low levels at which Tcl1 is expressed in mouse lymphocytes relative to human lymphocytes. 34,41 We also considered the possibility that the relatively modest phenotype seen in the Tcl1 Ϫ/Ϫ -deficient mice might represent a functional compensation by Tcl1 gene relatives. Tcl1 Ϫ/Ϫ mice and Tcl ϩ/ϩ /Tcl ϩ/Ϫ control mice immunized intravenously with SRBCs were bled at day 7 and day 15, and the serum samples analyzed for SRBC-specific IgM and IgG subclasses by ELISA (relative units/mL).…”

Section: Discussionmentioning

confidence: 99%

“…Since other members of the TCL1 family gene have been described in humans and mice, [34][35][36] we explored the possibility that these Tcl1 relatives could compensate in part for the effects of null Tcl1 alleles and thereby account for the modest immunodeficiency observed in the Tcl1 Ϫ/Ϫ mice. When transcription of the Tcl1b1-5 genes was evaluated in bone marrow, thymus, and spleen cells of Tcl1 Ϫ/Ϫ mice by seminested reverse transcriptase (RT)-PCR, we were unable to amplify Tcl1b1, b2, b4, and b5 transcripts from any of the lymphoid organs, whereas these transcripts were detectable in the analysis of a control egg library (data not shown), thereby suggesting that the Tcl1 Ϫ/Ϫ phenotype is not affected by a compensatory expression of neighboring Tcl1b genes.…”

Section: Hypersensitivity Of Tcr-bearing Thymocytes To Cd3 Ligation Inmentioning

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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“…More recently, TCL1 has been shown to also bind another type of PH domain (of the PNPase exoribonuclease) (French et al, 2006). Furthermore, the study of Tcl1 in murine systems has shown that Tcl1 is expressed in the ovary, testis and preimplantation embryos (Hallas et al, 1999;Narducci et al, 1997aNarducci et al, , b, 2002 and in murine embryonic stem (ES) cells (Ivanova et al, 2006). In particular, it plays an important role in the latter as, in Tcl1 À/À mice, preimplantation embryos are not able to progress beyond the 4-cell stage, in vitro (Narducci et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

The Tcl1 oncogene defines secondary hair germ cells differentiation at catagen–telogen transition and affects stem-cell marker CD34 expression

et al. 2009

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Overexpression of the TCL1 gene family plays a role in the onset of T-cell leukemias in mice and in humans. The Tcl1 gene is tightly regulated during early embryogenesis in which it participates in embryonic stem (ES)-cells proliferation and during lymphoid differentiation. Here, we provide evidences that Tcl1 is also important in mouse hair follicle (HF) and skin homeostasis. We found that Tcl1 À/À adult mice exhibit hair loss, leading to alopecia with extensive skin lesions. By analysing Tcl1 expression in the wild-type (wt) skin through different stages of hair differentiation, we observe high levels in the secondary hair germ (HG) cells and hair bulges, during early anagen and catagen-telogen transition phases. The loss of Tcl1 does not result in apparent skin morphological defects during embryonic development and at birth, but its absence causes a reduction of proliferation in anagen HFs. Importantly, we show the that absence of Tcl1 induces a significant loss of the stem-cell marker CD34 (but not a6-integrin) expression in the bulge cells, which is necessary to maintain stem-cell characteristics. Therefore, our findings indicate that Tcl1 gene(s) might have important roles in hair formation, by its involvement in cycling and self-renewal of transient amplifying (TA) and stem-cell (SC) populations.

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Genomic analysis of human and mouse TCL1 loci reveals a complex of tightly clustered genes

Cited by 55 publications

References 12 publications

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

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

The Tcl1 oncogene defines secondary hair germ cells differentiation at catagen–telogen transition and affects stem-cell marker CD34 expression

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