Nuclear Factors That Bind to the U3 Region of Two Murine Myeloid Leukemia-Inducing Retroviruses, Cas-Br-E and Graffi

Barat, Corinne; Rassart, Éric

doi:10.1006/viro.1998.9435

Cited by 6 publications

(5 citation statements)

References 65 publications

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“…These variations in latency are more likely explained by the presence of two direct repeats in the GV-1.2 LTR. Probably, this allows the binding of more transcription factors, making it globally more transcriptionally powerful as shown previously (4). GV-1.2 induces a higher percentage of T-cell leukemias.…”

Section: Graffi Is Extremely Multipotent and Induces Complex Leukemiasmentioning

confidence: 61%

“…This study reveals that the Graffi murine leukemia virus (MuLV) is a complex virus capable to induce a large spectrum of leukemias. It replicates efficiently in several cell types, as already suggested in studies of the LTR (3,4). It is multipotent and induces both lymphoid and nonlymphoid leukemia, including megakaryocytic leukemias, which are quite rare in MuLV-induced pathologies.…”

mentioning

confidence: 72%

“…The Graffi retroviruses are capable to infect a very large spectrum of cell types, and the major determinant is very likely due to its LTR. Indeed, we analyzed the Graffi LTR-driven transcriptional activity in several cell lines (4). The U3 region of GV-1.2 was found to be a very strong promoter in all the hematopoietic cell lines tested (erythroid, myeloid, and T-lymphoid).…”

Section: Graffi Is Extremely Multipotent and Induces Complex Leukemiasmentioning

confidence: 99%

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Novel Insights into the Pathogenesis of the Graffi Murine Leukemia Retrovirus

Voisin

Barat

Hoang

et al. 2006

J Virol

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The Graffi murine leukemia virus (MuLV) was isolated in 1954 by Arnold Graffi, who characterized it as a myeloid leukemia-inducing retrovirus. He and his team, however, soon observed the intriguing phenomenon of hematological diversification, which corresponded to a decrease of myeloid leukemias and an increase of other types of leukemias. Recently, we derived two different molecular clones corresponding to ecotropic nondefective genomes that were named GV-1.2 and GV-1.4. The induced leukemias were classified as myeloid based on morphological analysis of blood smears. In this study, we further characterized the two variants of the Graffi murine retrovirus, GV-1.2 and GV-1.4, in three different strains of mice. We show that the Graffi MuLV is a multipotent retrovirus capable of inducing both lymphoid (T-and B-cell) and nonlymphoid (myeloid, erythroid, megakaryocytic) leukemia. Many of these are very complex with concomitant expression of different hematopoietic lineages. Interestingly, a high percentage of megakaryocytic leukemias, a type of leukemia rarely observed with MuLVs, arise in the FVB/n strain of mice. The genetic backgrounds of the different strains of mice influence greatly the results. Furthermore, the enhancer region, different for GV-1.2 and GV-1.4, plays a pivotal role in the disease specificity: GV-1.2 induces more lymphoid leukemias, and GV-1.4 induces more nonlymphoid ones.About 50 years ago Arnold Graffi, at the Cancer Research Institute in Berlin, Germany, isolated a new retrovirus capable of inducing leukemia in a specific strain of mice, named AgnesBluhm, bred in his laboratory. Graffi (18) induced a large proportion of myeloid leukemias with a very high incidence of chloroleukemias (70%), characterized by a greenish coloration of the lymph nodes, and he classified the virus as a myeloid leukemia-inducing retrovirus.Working on better characterizing the pathogenesis of the virus, Graffi and his team were soon confronted with complex results. They observed the intriguing phenomenon of hematological diversification, which corresponded to a decrease in the percentage of chloroleukemias and an increase in other types of leukemias (11,12,19). This virus could induce multiple kinds of myeloid leukemias, from immature to differentiated forms, but also reticular, lymphoid, and erythroid leukemias and mixed forms (based on the classification at this time).It is very likely that Graffi was working at that time with a viral mixture. In 1993, Ru et al. (48) cloned two nondefective ecotropic retroviral genomes from NIH-3T3 cell lines chronically infected with the original Graffi acellular extract (a gift of Nathalie Teich). These two viral variants were called GV-1.2 and GV-1.4. The genomic restriction map and the sequences of their long terminal repeats (LTRs) (GenBank accession numbers L14415 and L14416 for GV-1.2 and GV-1.4, respectively) showed that they differ in the U3 region, one 60-bp segment being duplicated in GV-1.2 and not in GV-1.4. GV-1.2 induces disease with a shorter latency period. Based...

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Section: Graffi Is Extremely Multipotent and Induces Complex Leukemiasmentioning

confidence: 61%

mentioning

confidence: 72%

Section: Graffi Is Extremely Multipotent and Induces Complex Leukemiasmentioning

confidence: 99%

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Novel Insights into the Pathogenesis of the Graffi Murine Leukemia Retrovirus

Voisin

Barat

Hoang

et al. 2006

J Virol

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“…Second, a virus-flanking gene may be involved in murine but not human AML. This may apply to genes encoding transcription factors that activate promoter and enhancer elements in the virus LTR (17,18). Finally, some genes identified in mice may not be deregulated in human AML at the transcriptional but at the translational/posttranslational level or may be functionally altered due to mutations.…”

Section: Discussionmentioning

confidence: 99%

Significance of Murine Retroviral Mutagenesis for Identification of Disease Genes in Human Acute Myeloid Leukemia

et al. 2006

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Retroviral insertion mutagenesis is considered a powerful tool to identify cancer genes in mice, but its significance for human cancer has remained elusive. Moreover, it has recently been debated whether common virus integrations are always a hallmark of tumor cells and contribute to the oncogenic process. Acute myeloid leukemia (AML) is a heterogeneous disease with a variable response to treatment. Recurrent cytogenetic defects and acquired mutations in regulatory genes are associated with AML subtypes and prognosis. Recently, gene expression profiling (GEP) has been applied to further risk stratify AML. Here, we show that mouse leukemia genes identified by retroviral insertion mutagenesis are more frequently differentially expressed in distinct subclasses of adult and pediatric AML than randomly selected genes or genes located more distantly from a virus integration site. The candidate proto-oncogenes showing discriminative expression in primary AML could be placed in regulatory networks mainly involved in signal transduction and transcriptional control. Our data support the validity of retroviral insertion mutagenesis in mice for human disease and indicate that combining these murine screens for potential protooncogenes with GEP in human AML may help to identify critical disease genes and novel pathogenetic networks in leukemia. (Cancer Res 2006; 66(2): 622-6)

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“…Type B and type C viruses are known to act oncogenically by transactivation of genes near their integration site through promoters located in the viral LTRs. The U3 region of the type C LTR contains sequences for control and regulation of viral transcription with binding sites for several factors influencing tissue-specific expression and regulation of expression of both virus-encoded and cellular proteins (Fan, 1997 ; Barat & Rassart, 1998 ). Even in those cases where viral proteins are known to act as oncogenic transactivators, e.g.…”

Section: Discussionmentioning

confidence: 99%

A PCR primer system for detecting oncoretroviruses based on conserved DNA sequence motifs of animal retroviruses and its application to human leukaemias and lymphomas

Burmeister

Schwartz

Thiel

2001

Journal of General Virology

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Many C-and D-type retroviruses are known to cause a broad spectrum of malignant diseases in animals. Certain genome regions of these animal retroviruses are highly conserved between different animal species. It should be possible to detect new members of the retrovirus family with consensus PCR primers derived from these conserved sequence motifs. The consensus PCR primers developed in this study are generic enough to detect nearly all known oncogenic mammalian and avian exogenous C-and D-type retroviruses but do not amplify human endogenous retroviral sequences. In contrast to previous investigations, the present study involved highly stringent PCR conditions and truly generic PCR primers. Forty-four samples from patients with various immunophenotyped malignant diseases (acute and chronic T-/B-cell lymphocytic leukaemias, acute myeloid leukaemias, T-/B-cell lymphomas, chronic myeloproliferative disorders) and three cell lines (Hodgkin's lymphoma, Burkitt's lymphoma) have thus far been investigated using these PCR primers. The fact that no retroviruses have been found argues against an involvement of known animal oncoretroviruses or related hitherto undetected human retroviruses in the aetiopathogenesis of these diseases. The retrovirus detection system developed here may be used to confirm suspected retroviral involvement in other (malignant or nonmalignant) human diseases as well as to identify new animal retroviruses.

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Nuclear Factors That Bind to the U3 Region of Two Murine Myeloid Leukemia-Inducing Retroviruses, Cas-Br-E and Graffi

Cited by 6 publications

References 65 publications

Novel Insights into the Pathogenesis of the Graffi Murine Leukemia Retrovirus

Novel Insights into the Pathogenesis of the Graffi Murine Leukemia Retrovirus

Significance of Murine Retroviral Mutagenesis for Identification of Disease Genes in Human Acute Myeloid Leukemia

A PCR primer system for detecting oncoretroviruses based on conserved DNA sequence motifs of animal retroviruses and its application to human leukaemias and lymphomas

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