EVI1 Is Expressed in Megakaryocyte Cell Lineage and Enforced Expression of EVI1 in UT-7/GM Cells Induces Megakaryocyte Differentiation

Shimizu, Seiichi; Nagasawa, Toshiro; Katoh, Osamu; Komatsu, Norio; Yokota, Jun; Morishita, Kazuhiro

doi:10.1006/bbrc.2002.6693

Cited by 34 publications

(31 citation statements)

References 29 publications

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“…In vitro, EVI1 stimulated cell proliferation and inhibited differentiation and apoptosis in some experimental models, 12,16,20,[23][24][25][26][27][28][29][30][31] but elicited the opposite effects in others. 20,[31][32][33][34][35][36][37][38][39] This suggests that the fate of EVI1 overexpressing cells is influenced by lineage, maturation stage, cooperating molecular events, and/or environmental stimuli, and raises the possibility that it may be amenable to pharmacological modulation.…”

Section: Introductionmentioning

confidence: 99%

The oncogeneEVI1enhances transcriptional and biological responses of human myeloid cells toall-transretinoic acid

Steinmetz¹,

Hackl²,

Slabáková³

et al. 2014

Cell Cycle

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The product of the ecotropic virus integration site 1 (EVI1) gene, whose overexpression is associated with a poor prognosis in myeloid leukemias and some epithelial tumors, regulates gene transcription both through direct DNA binding and through modulation of the activity of other sequence specific transcription factors. Previous results from our laboratory have shown that EVI1 influenced transcription regulation in response to the myeloid differentiation inducing agent, all-trans retinoic acid (ATRA), in a dual manner: it enhanced ATRA induced transcription of the RARb gene, but repressed the ATRA induction of the EVI1 gene itself. In the present study, we asked whether EVI1 would modulate the ATRA regulation of a larger number of genes, as well as biological responses to this agent, in human myeloid cells. U937 and HL-60 cells ectopically expressing EVI1 through retroviral transduction were subjected to microarray based gene expression analysis, and to assays measuring cellular proliferation, differentiation, and apoptosis. These experiments showed that EVI1 modulated the ATRA response of several dozens of genes, and in fact reinforced it in the vast majority of cases. A particularly strong synergy between EVI1 and ATRA was observed for GDF15, which codes for a member of the TGF-b superfamily of cytokines. In line with the gene expression results, EVI1 enhanced cell cycle arrest, differentiation, and apoptosis in response to ATRA, and knockdown of GDF15 counteracted some of these effects. The potential clinical implications of these findings are discussed.

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Section: Introductionmentioning

confidence: 99%

The oncogeneEVI1enhances transcriptional and biological responses of human myeloid cells toall-transretinoic acid

Steinmetz¹,

Hackl²,

Slabáková³

et al. 2014

Cell Cycle

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“…Other in vitro studies show that EVI1 overexpression leads to impaired erythroid and megakaryocytic differentiation by GATA-1 inactivation. [44][45][46] However, in vivo, no abnormalities of erythroid cells were observed in Evi1 transgenic mice, although they did show a significant reduction in the number of erythroid colony-forming units, implying a defect of erythroid hematopoiesis affecting erythroid progenitor cells. 47 Therefore, overexpression of EVI1 might be involved in the development of AML of both acute erythroid and megakaryoblastic leukemia.…”

Section: Discussionmentioning

confidence: 94%

EVI1 overexpression in distinct subtypes of pediatric acute myeloid leukemia

et al. 2010

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Overexpression of the ecotropic virus integration-1 (EVI1) gene (EVI1 þ ), localized at chromosome 3q26, is associated with adverse outcome in adult acute myeloid leukemia (AML). In pediatric AML, 3q26 abnormalities are rare, and the role of EVI1 is unknown. We studied 228 pediatric AML samples for EVI1 þ using gene expression profiling and RQ-PCR. EVI1 þ was found in 20/213 (9%) of children with de novo AML, and in 4/8 with secondary AML. It was predominantly found in MLLrearranged AML (13/47), monosomy 7 (2/3), or FAB M6/7 (6/10), and mutually exclusive with core-binding factor AML, t(15;17), and NPM1 mutations. Fluorescent in situ hybridization (FISH) was performed to detect cryptic 3q26 abnormalities. However, none of the EVI1 þ patients harbored structural 3q26 alterations. Although significant differences in 4 years pEFS for EVI1 þ and EVI1À pediatric AML were observed (28%±11 vs 44%±4, P ¼ 0.04), multivariate analysis did not identify EVI1 þ as an independent prognostic factor. We conclude that EVI1 þ can be found in B10% of pediatric AML. Although EVI1 þ was not an independent prognostic factor, it was predominantly found in subtypes of pediatric AML that are related with an intermediate to unfavorable prognosis. Further research should explain the role of EVI1 þ in disease biology in these cases. Remarkably, no 3q26 abnormalities were identified in EVI1 þ pediatric AML.

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“…27 First, we examined the expression of TSLC1 in a series of hematopoietic cells by RT-PCR. 12 As shown in Figure 2A, TSLC1 was weakly expressed in erythrocytes, followed by neutrophils, monocytes, and B cells and was not expressed in T cells. We next examined TSLC1 expression in resting or activated CD4 ϩ T cells stimulated with PHA or an antibody mixture of anti-CD3 and anti-CD28.…”

Section: Ectopic Expression Of Tslc1 In Atl and Htlv-1-infected Cell mentioning

confidence: 87%

“…12 Briefly, human bone marrow mononuclear cells were isolated by Ficoll-Hypaque centrifugation from healthy volunteers. CD34 ϩ cells and megakaryocytes in bone marrow were isolated using DYNABEADS M-450 (Dynal) coupled with monoclonal antibodies against CD34 (QBWND10) and human platelet glycoprotein IIb/IIIa (GpIIb/IIIa; TP80; Seikagaku-Kogyo, Tokyo, Japan).…”

Section: Hematopoietic Cell Fractionsmentioning

confidence: 99%

Overexpression of a cell adhesion molecule, TSLC1, as a possible molecular marker for acute-type adult T-cell leukemia

Sasaki

Nishikata

Shiraga

et al. 2004

Blood

168

159

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Adult T-cell leukemia (ATL) caused by human T-cell leukemia virus type 1 (HTLV-1) infection, occurs in 2% to 4% of the HTLV-1 carriers with a long latent period, suggesting that additional alterations participate in the development of ATL. To characterize and identify novel markers of ATL, we examined the expression profiles of more than 12 000 genes in 8 cases of acute-type ATL using microarray. One hundred ninety-two genes containing interleukin 2 (IL-2) receptor ␣ were up-regulated more than 2-fold compared with CD4 ؉ and CD4 ؉ CD45RO ؉ T cells, and tumor suppressor in lung cancer 1 (TSLC1), caveolin 1, and prostaglandin D2 synthase showed increased expression of more than 30-fold.

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EVI1 Is Expressed in Megakaryocyte Cell Lineage and Enforced Expression of EVI1 in UT-7/GM Cells Induces Megakaryocyte Differentiation

Cited by 34 publications

References 29 publications

The oncogeneEVI1enhances transcriptional and biological responses of human myeloid cells toall-transretinoic acid

The oncogeneEVI1enhances transcriptional and biological responses of human myeloid cells toall-transretinoic acid

EVI1 overexpression in distinct subtypes of pediatric acute myeloid leukemia

Overexpression of a cell adhesion molecule, TSLC1, as a possible molecular marker for acute-type adult T-cell leukemia

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