SCL and LMO1 alter thymocyte differentiation: inhibition of E2A-HEB function and pre-Tα chain expression

Herblot, Sabine; Steff, Ann‐Muriel; Hugo, Patrice; Aplan, Peter D.; Hoang, Trang

doi:10.1038/77819

Cited by 195 publications

(272 citation statements)

References 46 publications

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“…We and others have shown that Tal1 expression perturbs thymocyte development by interfering with the expression of E47/HEB target genes (Herblot et al, 2000;O'Neil et al, 2004). Although Tal1 has been implicated in the proliferation of hematopoietic precursors (Green et al, 1991;Condorelli et al, 1997;Valtieri et al, 1998), this study suggests that Tal1 also stimulates cell cycle entry in preleukemic thymocytes.…”

Section: Discussionmentioning

confidence: 52%

“…We and others have shown that misexpression of Tal1 in the thymus alters thymocyte development by interfering with the expression of E47/HEB target genes including Rag1/2, Pre-Ta, CD4, CD5, CD3 and the TCRabchains (Herblot et al, 2000;O'Neil et al, 2001O'Neil et al, , 2004. Although Tal1 induces leukemia in mice, it does so after a long latency revealing that additional genetic events are required (Condorelli et al, 1996;Kelliher et al, 1996).…”

Section: Introductionmentioning

confidence: 93%

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p16Ink4a or p19Arf loss contributes to Tal1-induced leukemogenesis in mice

et al. 2006

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Analysis of the INK4A/ARF locus in human T-ALL patients revealed frequent deletions in exon 2, the exon common to both p16 INK4A and p14 ARF . Other studies have described selective deletion of exon 1b of p14 ARF or methylation of the p16 INK4A promoter. Therefore, it is unclear from these studies whether loss of p16 INK4A and/or p14 ARF contributes to the development of T-ALL. To elucidate the relative contribution of the ink4a/arf locus to T-cell leukemogenesis, we mated our tal1 transgenic mice to ink4a/arfÀ/À, p16 ink4a À/À, and p19 arf À/À mice and generated tal1/ink4a/arf þ /À, tal1/p16 ink4a þ /À, and tal1/p19 arf þ /À mice. Each of these mice developed T-cell leukemia rapidly, indicating that loss of either p16 ink4a or p19 arf cooperates with Tal1 to induce leukemia in mice. Preleukemic studies reveal that Tal1 expression stimulates entry into the cell cycle and thymocyte apoptosis in vivo. Interestingly, mice expressing a DNA-binding mutant of Tal1 do not exhibit increases in S phase cells. The S phase induction is accompanied by an increase in thymocyte apoptosis in tal1 transgenic mice. Whereas apoptosis is reduced to wild-type levels in tal1/ink4a/ arfÀ/À mice, S phase induction remains unaffected. Thus, Tal1 stimulates cell cycle entry independent of the ink4a/arf locus, but its ability to induce apoptosis is Ink4a/Arfdependent.

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Section: Discussionmentioning

confidence: 52%

Section: Introductionmentioning

confidence: 93%

p16Ink4a or p19Arf loss contributes to Tal1-induced leukemogenesis in mice

et al. 2006

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“…Tal1 is a protein binding partner of Lmo2 (Larson et al, 1996;Valge-Archer et al, 1994;Wadman et al, 1994Wadman et al, , 1997 suggesting that protein ± protein interaction plays a key role in T-ALL (Rabbitts, 1998). Similar e ects of Lmo1 and Tal1 transgenes on T cell development have been described (Chervinsky et al, 1999;Herblot et al, 2000).…”

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confidence: 75%

T cell tumorigenesis in Lmo2 transgenic mice is independent of V-D-J recombinase activity

2001

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The LMO2 gene is involved in T-cell acute leukaemia (T-ALL) in children with chromosomal translocations t(11;14)(p13;q11) or (7;11)(q35;p13). Transgenic expression of Lmo2 in T cells results in clonal tumours with long latency indicating that mutations in other genes are required for the development of overt tumours. RAG V-D-J recombinase can mediate genetic transposition and thus might create the secondary mutations necessary for T-ALL. Tumour development was compared in Lmo2 transgenic mice in the presence or absence of the Rag1 gene. No di erence was observed in the rate of tumour formation nor in tumour histology in Lmo2-transgenic mice with or without Rag1. We conclude that, in this model, RAG recombinase is not a major mediator of mutations needed for T cell tumorigenesis and that antigen binding (1994)). The LIM-only genes LMO1 and LMO2 were discovered by their activation through the T cell-speci®c translocations t(11;14)(p15;q11) and t(11;14)(p13;q11) respectively (Rabbitts, 1998) (LMO2 is also activated by a variant translocation t(7;11)(q35;p13) in a subset of T-ALL (Sanchez-Garcia et al., 1991). Mouse models of T-ALL mediated by Lmo1 or Lmo2 demonstrate that transgenic mice expressing these genes develop clonal T cell tumours after several months (Aplan et al

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“…The LIM domain does not directly interact with DNA, but acts as an adaptor molecule for transcription factors facilitating assembly of large transcriptional complexes (Breen et al, 1998;Jurata et al, 1998;Sugihara et al, 1998). LMO1 and LMO2 have been shown to specify neuronal and haematopoietic cell lineages in combination with their transcription partners (Hinks et al, 1997;Yamada et al, 1998;Herblot et al, 2000). Misexpression of these genes by chromosomal translocation abrogates proper differentiation of cells and is oncogenic within T cells (Boehm et al, 1991;Royer-Pokora et al, 1991).…”

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confidence: 99%

The LIM-only protein, LMO4, and the LIM domain-binding protein, LDB1, expression in squamous cell carcinomas of the oral cavity

et al. 2003

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Carcinoma cells can lose their epithelial cell characteristics and dedifferentiate into a fibroblast-like cell during progression of a neoplasm. Aberrant expression of oligomeric transcriptional complexes contributes to progression of carcinomas. Although individual transcription factors initiating progression remain unknown, LIM-only protein (LMO) and LIM-domain binding protein (LDB) negatively regulate breast carcinoma cell differentiation. In this study, we investigated the expression of LMO4 and LDB in squamous cell carcinomas of the oral cavity. LMO4 mRNA was amplified in four of six carcinoma tissues and eight of 12 carcinoma cell lines, and LDB1 in three carcinoma tissues and 11 cell lines examined. Immunoprecipitation studies revealed that LMO4 and LDB1 interact with each other in the nuclear milieu of the carcinoma cells indicating the presence of an LMO4-LDB1-mediated transcription complex. Both LMO4 and LDB1 proteins were preferentially localised in the nuclei of carcinoma cells at the invasive front and the immunoreactivity was increased in less-differentiated carcinoma tissues (Po0.01). Carcinoma cells metastasised to the cervical lymph nodes with increased immunoreactivity compared to the primary site of neoplasm (Po0.05). These data suggest that the LMO4 -LDB1 complexes may be involved in carcinoma progression possibly through dedifferentiation of squamous carcinoma cells of the oral cavity.

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SCL and LMO1 alter thymocyte differentiation: inhibition of E2A-HEB function and pre-Tα chain expression

Cited by 195 publications

References 46 publications

p16Ink4a or p19Arf loss contributes to Tal1-induced leukemogenesis in mice

p16Ink4a or p19Arf loss contributes to Tal1-induced leukemogenesis in mice

T cell tumorigenesis in Lmo2 transgenic mice is independent of V-D-J recombinase activity

The LIM-only protein, LMO4, and the LIM domain-binding protein, LDB1, expression in squamous cell carcinomas of the oral cavity

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