Retroviral activation of a novel gene encoding a zinc finger protein in IL-3-dependent myeloid leukemia cell lines

Morishita, Kazuhiro; Parker, D S; Mucenski, Michael L.; Jenkins, Nancy A.; Copeland, Neal G.; Ihle, James N.

doi:10.1016/s0092-8674(88)91175-0

Cited by 407 publications

(300 citation statements)

References 64 publications

Supporting

Mentioning

294

Contrasting

Order By: Relevance

“…The EVI1 gene, and its longer splicing variant EVI1-MDS1, are products of MECOM (MDS1 and EVI1 complex) located on chromosome 3q26.2 that encodes a highly conserved proto-oncoprotein in humans, which may function as a transcriptionregulatory protein. 12 EVI1 encodes a 1051 aminoacid zinc-finger protein of 145 kDa. It has been shown that EVI1 affects multiple signaling pathways, including the TGF-b, c-Jun N-terminal kinase-1 (JNK1), and activator protein-1 (AP1) pathways.…”

Section: Discussionmentioning

confidence: 99%

De novo acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2): a clinicopathologic and cytogenetic study of an entity recently added to the WHO classification

et al. 2011

View full text Add to dashboard Cite

Acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2) is a rare type of leukemia recently added to the World Health Organization (WHO) classification scheme. In this study, we analyzed the clinicopathologic and cytogenetic features of 30 cases of de novo acute myeloid leukemia with inv(3)/t(3;3). The median patient age was 53 years (range, 27-77 years). The platelet count was variable (range, 21-597 Â 10 9 /l, median: 128 Â 10 9 /l), and two (6.7%) patients presented with thrombocytosis (4450 Â 10 9 /l). Morphologically, these neoplasms showed a spectrum of findings. Myelomonocytic differentiation was most common in 11 (37%) cases. Morphological evidence of dysplasia was observed in at least one lineage in 23 of 25 (92%) cases in which maturing elements could be assessed. In all, 5 (17%) patients had isolated inv(3) or t(3;3) and 25 (83%) patients had additional cytogenetic abnormalities, most often monosomy 7 (40%). Eleven (37%) patients had a complex karyotype (Z3 additional abnormalities). FLT3 gene mutation by internal tandem duplication was identified in 2 of 23 (9%) cases assessed. No clinical, pathological, or cytogenetic features independent of inv(3) or t(3;3) correlated with a worse outcome. However, patients treated with allogeneic stem cell transplantation (n ¼ 11) had a significantly better survival than did those treated with chemotherapy alone (n ¼ 17) (13.8 vs 8.0 months, P ¼ 0.041). We conclude that de novo acute myeloid leukemia associated with inv(3)/t(3;3) is an aggressive type of leukemia regardless of morphological or karyotypic findings, supporting the inclusion of this disease as a specific entity defined by inv(3)/t(3;3) in the WHO classification. Allogeneic stem cell transplantation seems to improve outcome in patients with this disease.

show abstract

Section: Discussionmentioning

confidence: 99%

De novo acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2): a clinicopathologic and cytogenetic study of an entity recently added to the WHO classification

et al. 2011

View full text Add to dashboard Cite

show abstract

“…9 EVI1 encodes a nuclear DNA binding protein 9,10 with two domains containing two sets of seven and three repeats of the Cys 2 Hys 2 type of zinc finger motif. 2 The domain consisting of seven zinc finger repeats is localized in the amino terminus whereas the second domain, containing three zinc finger motifs, is found toward the carboxyl terminus (Figure 1a). This type of zinc finger is frequently seen in transcription factors involved in other leukemia-associated chromosomal translocations.…”

Section: Evi1 Is a Sequence-specific Dna-binding Proteinmentioning

confidence: 99%

“…1 Subsequently, it was shown in the mouse that viral insertions in this locus activated the expression of a novel gene which was called Evi1. 2 The Evi1 locus was later mapped to murine chromosome 3. 3 In addition, analysis of Cas-Br-E MuLV integration sites showed that integration at the Evi1 locus induced myeloid leukemia in NIH/Swiss and NSF mice.…”

Section: Introductionmentioning

confidence: 99%

“…1,3,4 Retroviral insertions into the murine Evi1 locus occur almost exclusively in two well-defined regions upstream of the gene, and result in the inappropriate expression of Evi1 through promoter activation by the retroviral long terminal repeat (LTR). 2 The preferential integration site closest to the coding region of the gene is either within a 2 kb stretch of DNA which encompasses exon 1 of Evi1, or between noncoding exons 1 and 2 of the gene, 2 and it was suggested that Evi1 transcription could be initiated from the retroviral promoter inserted into this region. Evi1 expression may also be activated from a second insertion site in the Cb-1/Fim3 locus, located 90 kb upstream of exon 1 and identified independently in two laboratories.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The EVI1 gene in myeloid leukemia

Nucifora

1997

Leukemia

119

View full text Add to dashboard Cite

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.

show abstract

“…Retroviral activation of the ecotropic viral integration site 1 (Evi1) results in leukemia in mice (Morishita et al, 1988). Evi1 activation has been implicated in hematopoietic malignancies in humans (Bartholomew and Ihle, 1991;Ogawa et al, 1996), and the oncogenic role of Evi1 has been studied extensively in myeloid and lymphoid leukemia.…”

Section: Introductionmentioning

confidence: 99%

Evi1 is a survival factor which conveys resistance to both TGFβ- and taxol-mediated cell death via PI3K/AKT

Liu

Chen

et al. 2006

Oncogene

View full text Add to dashboard Cite

Retroviral activation of a novel gene encoding a zinc finger protein in IL-3-dependent myeloid leukemia cell lines

Cited by 407 publications

References 64 publications

De novo acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2): a clinicopathologic and cytogenetic study of an entity recently added to the WHO classification

De novo acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2): a clinicopathologic and cytogenetic study of an entity recently added to the WHO classification

The EVI1 gene in myeloid leukemia

Evi1 is a survival factor which conveys resistance to both TGFβ- and taxol-mediated cell death via PI3K/AKT

Contact Info

Product

Resources

About