Molecular Analysis of Evi1, a Zinc Finger Oncogene Involved in Myeloid Leukemia

Lopingco, M. C.; Perkins, Archibald S.

doi:10.1007/978-3-642-85232-9_21

Cited by 18 publications

(15 citation statements)

References 51 publications

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“…32 In contrast, studies using CAT reporters that contained either the first or second EVI1 target sites upstream of the HSVtk promoter found that EVI1 dramatically expressed the activity of these reporters. 28,33 More recently, studies by Bartholomew et al 34 showed that EVI1 represses synthetic promoters in which the zinc fingers consensus site was cloned upstream of the herpes simplex virus (HSV) thymidine kinase (tk) promoter or of the adenovirus minimal promoter, confirming the role of EVI1 as transcriptional repressor. In addition, these investigators showed that the repression function is localized in a stretch of proline-rich residues located between the two groups of zinc fingers (Figure 1a), and it can be completely abolished by an internal deletion spanning the proline-rich stretch.…”

Section: Evi1 Expression and Functionmentioning

confidence: 96%

The EVI1 gene in myeloid leukemia

Nucifora

1997

Leukemia

118

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Leukemia is an acquired genetic disease caused by the accumulation of chromosomal abnormalities which modify either the biochemical property or the level of expression of proteins. Frequent genetic abnormalities identified in human leukemia are chromosomal rearrangements such as chromosomal translocations and inversions. Chromosome band 3q26 is the site of the breakpoint of recurring translocations and inversions observed in patients with myeloid leukemias. Two genes located at 3q26 have been implicated in development or progression of myeloid leukemia. They are MDS1 and EVI1. MDS1, first identified as part of a fusion transcript resulting from the t(3;21)(q26;q22), encodes a small protein of unknown function. EVI1 encodes a zinc finger protein inappropriately overexpressed by chromosomal rearrangements (in man) or by retroviral insertion (in the mouse). Both genes are rearranged by the t(3;21)(q26;q22) and by the t(3;12)(p13;q22). As a result of the translocation, they are expressed as fusion genes either with AML1 or with TEL. EVI1 and MDS1 are unusual in that they can either encode separate proteins, or they can be expressed as one protein which we named MDS1/EVI1. EVI1 and MDS1/EVI1 have opposite functions as transcription factors. In this report, we review the current information on the two genes, and on their involvement in myeloid leukemia.

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Section: Evi1 Expression and Functionmentioning

confidence: 96%

The EVI1 gene in myeloid leukemia

Nucifora

1997

Leukemia

118

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“…Evi-1 is a zinc finger containing proto-oncoprotein implicated in the leukemic transformation of hemopoeitic cells (Lopingco and Perkins 1996). Evi-1 was initially shown to bind to Smad3 and inhibit its ability to bind to DNA, preventing TGF␤-induced growth inhibition (Kurokawa et al 1998).…”

Section: Constraining Smad Transcriptional Functionsmentioning

confidence: 99%

“…Evi-1 is a component of the AML/Evi-1 fusion gene generated by a 3;21 chromosomal translocation (Lopingco and Perkins 1996). These fusions express the entire Evi-1 protein fused to the DNA-binding (Runt) domain of AML1.…”

Section: Constraining Smad Transcriptional Functionsmentioning

confidence: 99%

Smad transcription factors

Massagué

Seoane²,

Wotton³

2005

Genes Dev.

2,148

2,107

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Smad transcription factors lie at the core of one of the most versatile cytokine signaling pathways in metazoan biology-the transforming growth factor-␤ (TGF␤) pathway. Recent progress has shed light into the processes of Smad activation and deactivation, nucleocytoplasmic dynamics, and assembly of transcriptional complexes. A rich repertoire of regulatory devices exerts control over each step of the Smad pathway. This knowledge is enabling work on more complex questions about the organization, integration, and modulation of Smad-dependent transcriptional programs. We are beginning to uncover self-enabled gene response cascades, graded Smad response mechanisms, and Smad-dependent synexpression groups. Our growing understanding of TGF␤ signaling through the Smad pathway provides general principles for how animal cells translate complex inputs into concrete behavior.As evolution unfolded and multicellular life forms emerged, so did the need for tight control over the ability of individual cells to move, divide, differentiate, and organize. Intricate intercellular communication systems evolved to ensure the proper behavior of individual cells in the context of the whole organism. Among these forms of communication, one of the most prevalent involves secretory polypeptides that are recognized by membrane receptors coupled to transcriptional regulatory factors. With its 42 members in the human genome, seven in Drosophila, and four in Caenorhabditis elegans, the transforming growth factor-␤ (TGF␤) family is one of the most prominent representatives of this class of molecules. TGF␤ and its family members-the nodals, activins, bone morphogenetic proteins (BMPs), myostatins, anti-Muellerian hormone (AMH), and others-exert profound effects on cell division, differentiation, migration, adhesion, organization, and death.

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“…EVI1 gene rearrangements account for approximately 5% of cytogenetic abnormalities in these disease entities. 2 Patients with an EVI1 rearrangement have distinct clinical features, such as marked hyperplasia with dysplasia of the megakaryocytes 3 and, in some cases, hyperthrombocytosis. 4 These 3q26 chromosomal aberrations confer an adverse prognosis and contribute to ectopic expression of either full length or truncated EVI1 transcripts, or to the formation of EVI1 fusion genes.…”

Section: Introductionmentioning

confidence: 99%

EVI1 overexpression in t(3;17) positive myeloid malignancies results from juxtaposition of EVI1 to the MSI2 locus at 17q22

Weer

Speleman²,

Cauwelier³

et al. 2008

Haematologica

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Chromosomal translocations involving the EVI1 locus are a recurrent finding in myeloid leukemia and are associated with poor prognosis. In this study, we performed a detailed molecular characterization of the recurrent translocation t(3;17)(q26;q22) in 13 hematologic malignancies. The EVI1 gene locus was rearranged in all 13 patients and was associated with EVI1 overexpression. In 9 out of 13 patients, the 17q breakpoints clustered in a 250 kb region on band 17q22 encompassing the MSI2 (musashi homologue 2) gene.Expression analyses failed to demonstrate ectopic MSI2 expression or the presence of an MSI2/EVI1 fusion gene. In conclusion, we show for the first time that the t(3;17) is indeed a recurrent chromosomal aberration in myeloid malignancies. In keeping with findings in other recurrent 3q26 rearrangements, overexpression of the EVI1 gene appears to be the major contributor to leukemogenesis in patients with a t(3;17).

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Molecular Analysis of Evi1, a Zinc Finger Oncogene Involved in Myeloid Leukemia

Cited by 18 publications

References 51 publications

The EVI1 gene in myeloid leukemia

The EVI1 gene in myeloid leukemia

Smad transcription factors

EVI1 overexpression in t(3;17) positive myeloid malignancies results from juxtaposition of EVI1 to the MSI2 locus at 17q22

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