TCL1 oncogene expression in AIDS-related lymphomas and lymphoid tissues

Teitell, Michael A.; Damore, Michael A.; Sulur, Giri; Turner, Devin E.; Stern, Marc‐Henri; Said, Jonathan; Denny, Christopher T.; Wall, Randolph

doi:10.1073/pnas.96.17.9809

Cited by 73 publications

(95 citation statements)

References 63 publications

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“…Three transgenic mouse models carrying TCL1 under the control of T-and B-cell promoters develop mature T-and B-cell leukemia, thus confirming the oncogenic role of TCL1 overexpression (Virgilio et al, 1998;Bichi et al, 2002;Hoyer et al, 2002). Moreover, TCL1 has been shown to be constitutively expressed in a tightly regulated manner in lymphoid cells of B and T origins (Narducci et al, 1997a, b;Takizawa et al, 1998;Teitell et al, 1999;Kang et al, 2005). Functionally, Tcl1 exerts its function by binding the pleckstrin domain of AKT proteins, thereafter increasing AKT kinase activity and enhancing AKT nuclear translocation in vitro (Laine et al, 2000;Pekarsky et al, 2000;Kunstle et al, 2002) and in vivo (Zanesi et al, 2006).…”

Section: Introductionmentioning

confidence: 89%

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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Section: Introductionmentioning

confidence: 89%

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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“…One group, using PCR-based suppression subtractive hybridization, determined that lymph-node-based AIDS-related diffuse large B-cell lymphoma overexpressed the proto-oncogene TCL1 (T-cell leukemia-1), which was absent in non-AIDS diffuse large B-cell lymphoma. 32 The authors postulated that the deleterious effects of HIV on the host immune system could be responsible for the different clinical outcomes in AIDS vs non-AIDS patients with lymphoma. 20,32,33 In the context of B-lymphocyte development, an early immunohistochemical study of AIDS-related lymphomas proposed three phenotypic patterns corresponding to centroblasts, late germinal center/early postgerminal center B cells, and postgerminal center Bcells.…”

Section: Aids and Non-aids Diffuse Large B-cell Lymphoma R Madan Et Almentioning

confidence: 99%

“…32 The authors postulated that the deleterious effects of HIV on the host immune system could be responsible for the different clinical outcomes in AIDS vs non-AIDS patients with lymphoma. 20,32,33 In the context of B-lymphocyte development, an early immunohistochemical study of AIDS-related lymphomas proposed three phenotypic patterns corresponding to centroblasts, late germinal center/early postgerminal center B cells, and postgerminal center Bcells. 34 Another study, which included cases of both AIDS-related diffuse large B-cell lymphoma and Burkitt lymphoma, has suggested that there may be a shift away from the more chemoresistant lymphomas of postgerminal center origin because of the better immune function conferred by highly active antiretroviral therapy.…”

Section: Aids and Non-aids Diffuse Large B-cell Lymphoma R Madan Et Almentioning

confidence: 99%

AIDS and non-AIDS diffuse large B-cell lymphomas express different antigen profiles

et al. 2006

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Based on gene expression profiling, diffuse large B-cell lymphomas arising in immunocompetent patients can be divided into germinal center and activated B-cell types. Since little is known about acquired immunodeficiency syndrome associated diffuse large B-cell lymphomas, we tested whether the protein expression of germinal center and activated B-cell markers differed between acquired immunodeficiency syndrome (AIDS) vs non-AIDS diffuse large B-cell lymphomas. We immunohistochemically stained tissue microarrays of 39 de novo diffuse large B-cell lymphomas: 12 AIDS associated and 27 non-AIDS, with germinal center (BCL6, CD10, CyclinH) and activated B-cell markers (MUM1, CD138, PAK1, CD44, BCL2). We scored each case for percent positive cells (0-19% ¼ 0; 20-49% ¼ 1; 50-100% ¼ 2). The activated B-cell and germinal center summation scores of each case were used as (x, y) coordinate data points to construct two-dimensional contour-frequency plots. The contour plot of non-AIDS diffuse large B-cell lymphomas showed two distinct clusters: a cluster with a high germinal center phenotype (cluster 1) and a cluster with a high activated B-cell phenotype (cluster 3). In contrast, the AIDS-related diffuse large B-cell lymphomas formed a single aggregate (cluster 2) (P ¼ 0.02, Fisher exact test). When the contour plots of the AIDS-related and the non-AIDS cases were superimposed, cluster 2 of the AIDS cases expressed an intermediate germinal center/activated B-cell phenotype compared to clusters 1 and 3 of the non-AIDS diffuse large B-cell lymphomas. Our results confirm that non-AIDS diffuse large B-cell lymphomas segregate into two groups with either germinal center or activated B-cell phenotype. We report the new finding that the AIDS status of the patient predicts the immunophenotype of the diffuse large B-cell lymphomas. We also describe a novel method for displaying immunohistochemical expression data using twodimensional contour-frequency plots. Materials and methods Lymphoma SamplesWe performed a retrospective study of 56 diffuse large B-cell lymphomas (23 AIDS-related and 33 non-AIDS) that were retrieved from the archives of

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“…Dysregulated expression of TCL1 is a frequent molecular alteration in non-Hodgkin lymphomas (NHLs) that arise by transformation of germinal center (GC) B-cells (Teitell et al, 1999;Narducci et al, 2000;Said et al, 2001). Supporting an etiologic role in transformation, dysregulated expression of TCL1 in transgenic mouse B-cells throughout all stages of B-cell development promotes a spectrum of GC B-cell lymphoma subtypes that metastasize (Hoyer et al, 2002;Shen et al, 2006) or aggressive marginal zone-derived B-cell chronic lymphocytic leukemia (Bichi et al, 2002;Klein and Dalla-Favera, 2005;Yan et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Global DNA methylation profiling reveals silencing of a secreted form of Epha7 in mouse and human germinal center B-cell lymphomas

et al. 2007

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Most human lymphomas originate from transformed germinal center (GC) B lymphocytes. While activating mutations and translocations of MYC, BCL2 and BCL6 promote specific GC lymphoma subtypes, other genetic and epigenetic modifications that contribute to malignant progression in the GC remain poorly defined. Recently, aberrant expression of the TCL1 proto-oncogene was identified in major GC lymphoma subtypes. TCL1 transgenic mice offer unique models of both aggressive GC and marginal zone B-cell lymphomas, further supporting a role for TCL1 in B-cell transformation. Here, restriction landmark genomic scanning was employed to discover tumor-associated epigenetic alterations in malignant GC and marginal zone B-cells in TCL1 transgenic mice. Multiple genes were identified that underwent DNA hypermethylation and decreased expression in TCL1 transgenic tumors. Further, we identified a secreted isoform of EPHA7, a member of the Eph family of receptor tyrosine kinases that are able to influence tumor invasiveness, metastasis and neovascularization. EPHA7 was hypermethylated and repressed in both mouse and human GC B-cell non-Hodgkin lymphomas, with the potential to influence tumor progression and spread. These data provide the first set of hypermethylated genes with the potential to complement TCL1-mediated GC B-cell transformation and spread.

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TCL1 oncogene expression in AIDS-related lymphomas and lymphoid tissues

Cited by 73 publications

References 63 publications

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

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

AIDS and non-AIDS diffuse large B-cell lymphomas express different antigen profiles

Global DNA methylation profiling reveals silencing of a secreted form of Epha7 in mouse and human germinal center B-cell lymphomas

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