The role of Fli-1 in normal cell function and malignant transformation

Truong, Amandine; Ben‐David, Yaacov

doi:10.1038/sj.onc.1204042

Cited by 111 publications

(87 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…FLI1 is involved in the oncogenic fusion-protein EWS-FLI1 of Ewing sarcoma, in which its transcriptional activity is pivotal. 33 In mice, FLI1 regulates B-cell differentiation, proliferation, and apoptosis and contributes to the control of marginal zone and follicular B-cell development. 34 In our study, the 11q24.3 gain was observed in both GCB-and ABC-DLBCL.…”

Section: Discussionmentioning

confidence: 99%

Deregulation of ETS1 and FLI1 contributes to the pathogenesis of diffuse large B-cell lymphoma

Bonetti

Testoni

Scandurra

et al. 2013

Blood

View full text Add to dashboard Cite

Key Points• A recurrent gain of a region of chromosome 11 (11q24.3) occurs in up to one-quarter of cases of diffuse large B-cell lymphoma.• ETS1 and FLI1 genes are overexpressed and determine proliferation, survival, and differentiation arrest of the lymphoma cells.Diffuse large B-cell lymphoma (DLBCL) is the most common form of human lymphoma. DLBCL is a heterogeneous disease characterized by different genetic lesions. We herein report the functional characterization of a recurrent gain mapping on chromosome 11q24.3, found in 23% of 166 DLBCL cases analyzed. The transcription factors ETS1 and FLI1, located within the 11q24.3 region, had significantly higher expression in clinical samples carrying the gain. Functional studies on cell lines showed that ETS1 and FLI1 cooperate in sustaining DLBCL proliferation and viability and regulate genes involved in germinal center differentiation. Taken together, these data identify the 11q24.3 gain as a recurrent lesion in DLBCL leading to ETS1 and FLI1 deregulated expression, which can contribute to the pathogenesis of this disease. (Blood. 2013;122(13):2233-2241) IntroductionDiffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, accounting for 25% to 30% of adult cases in western countries, and it is characterized by heterogeneous histopathological, biological, and clinical features.1 DLBCL has been molecularly classified in at least 3 subtypes, reflecting different stages of B-cell differentiation: germinal center B-cell-like DLBCL (GCB) from germinal center (GC) centroblasts, activated B-cell-like DLBCL (ABC) from GC cells undergoing plasmacytic differentiation, and an intermediate type 3 DLBCL. 2 Physiological GC B-cell differentiation requires a complex transcriptional program and DLBCL displays recurrent genetic abnormalities that typically circumvent this normal genetic program, allowing the neoplastic B cells to avoid plasmacytic differentiation and evade apoptosis.2 Briefly, chromosomal translocations involving the BCL2 oncogene and mutations of the EZH2 methyltransferase are almost exclusively observed in GCB DLBCL, 3 whereas ABC DLBCL are preferentially associated with a disruption of terminal B-cell differentiation program (ie, PRDM1 inactivation and BCL6 deregulation) 4,5 and constitutive activation of the nuclear factor kB (NF-kB) transcription pathway (most commonly via somatic mutations of TNFAIP3, CARD11, CD79B, and MYD88). [6][7][8] Other recurrent lesions can be found in all the DLBCL subtypes, including inactivation of histone and/or chromatin modifying genes CREBBP, EP300, and MLL2 9,10 and of genes involved in immune recognition, such as b2-microglobulin and CD58. 11 It is likely that additional, undescribed genetic defects may also contribute to the pathogenesis of DLBCL.In the present study, aimed to identify new recurrent genetic defects in DLBCL, we performed genomic profiling analysis on 166 DLBCL samples, which enabled us to characterize a new recurrent lesion on chromosome 11q24.3 occurring in up to onequarter of...

show abstract

Section: Discussionmentioning

confidence: 99%

Deregulation of ETS1 and FLI1 contributes to the pathogenesis of diffuse large B-cell lymphoma

Bonetti

Testoni

Scandurra

et al. 2013

Blood

View full text Add to dashboard Cite

show abstract

“…1 Its clinical role is most apparent in the human Ewing's sarcoma/ primitive neuroectodermal tumor (ES/PNET) category, wherein FLI-1 is the target of a characteristic balanced chromosomal translocation t(11;22) (q24:q12) which results in the production of the EWS/FLI-1 fusion gene. The resultant EWS/FLI-1 chimeric protein includes the N-terminal transactivation domain of EWS and the C-terminal DNAbinding domain of FLI-1.…”

mentioning

confidence: 99%

Utility of the immunohistochemical detection of FLI-1 expression in round cell and vascular neoplasm using a monoclonal antibody

et al. 2004

View full text Add to dashboard Cite

FLI-1 nuclear transcription factor has been proposed as a useful tool in the differential diagnosis of small round cell sarcomas. Recently, FLI-1 has been reported as the first nuclear marker of endothelial differentiation. However, its clinical use has been hampered by major interpretation problems, due to the presence of background staining as well as staining variation between different lots of the same antiserum. In this study, a novel monoclonal antibody raised against the carboxyl terminal of the FLI-1 protein (clone GI146-222, BD Pharmingen) was tested in a series of small round cell and vascular neoplasms. Furthermore, in order to assess FLI-1 specificity, we analyzed its expression in a series of common epithelial and nonepithelial malignancies. In total, 15 Ewing's sarcomas, 10 rhabdomyosarcomas, 5 desmoplastic small round cell tumors, 10 synovial sarcomas, 10 high-grade pleomorphic sarcomas, 10 malignant melanomas, 5 Merkel's carcinomas, 10 colonic adenocarcinomas, 10 breast carcinomas, 10 lung adenocarcinomas, 20 angiosarcomas, 5 epithelioid hemangioendotheliomas, 10 Kaposi's sarcomas and 10 benign hemangiomas, were stained. A strong FLI-1 immunoreactivity was detected in all Ewing's sarcomas and vascular neoplasms, highlighting the high sensitivity of FLI-1 monoclonal antibody. However, 2/5 Merkel's carcinomas and 1/10 malignant melanomas showed a strong nuclear immunostaining, suggesting that FLI-1 may not be so helpful in the differential diagnosis of cutaneous Ewing's sarcoma. In addition, a weak immunoreactivity was found in 3/5 Merkel cell carcinomas, 3/10 synovial sarcomas, 5/10 malignant melanomas, 6/10 lung adenocarcinomas and in 1/10 breast carcinomas. In contrast, all the rhabdomyosarcomas, desmoplastic small round cell tumors, high-grade pleomorphic sarcomas and colonic adenocarcinomas tested were negative. Importantly, in contrast with previous studies, no background staining was observed. Our results indicate that FLI-1 monoclonal antibody can be reliably applied to the differential diagnosis of small round cell neoplasms of soft tissue, and confirm its important role as nuclear marker of endothelial differentiation, mainly helpful in those cases in which technical artifacts are seen by using the traditional membranous and cytoplasmic endothelial markers. 2 The EWS/FLI-1 chimeric protein binds DNA with the same affinity as FLI-1, but EWS/FLI-1 transcriptional activation of the target genes is much more efficient.3 ES/PNET belongs to a heterogeneous group of mesenchymal neoplasms featuring round cell morphology and therefore collectively known as small round cell sarcomas. Alveolar rhabdomyosarcoma (RMS), desmoplastic small round cell tumor (DSRCT), mesenchymal chondrosarcoma and poorly differentiated synovial sarcoma (SS) also belong to

show abstract

“…20 Fli1, a member of the Ets family of transcription factors, has been shown to play roles in hematopoiesis, embryonic development, and vasculogenesis. [21][22][23][24] Collective evidence indicates that Ets transcription factors are the important mediators of cellular programs involved in extracellular matrix degradation, 25 and are frequently dysregulated in diseases characterized by abnormal matrix turnover, including invasive tumors and arthritis. 26 In contrast, the specific role(s) of the Ets factors in the maintenance of collagen level homeostasis in healthy skin and their possible role in fibroproliferative disorders, including SSc, has not yet been adequately assessed.…”

mentioning

confidence: 99%

Persistent Down-Regulation of Fli1, a Suppressor of Collagen Transcription, in Fibrotic Scleroderma Skin

Kubo

Czuwara-Ladykowska

Moussa

et al. 2003

The American Journal of Pathology

158

143

View full text Add to dashboard Cite

show abstract

The role of Fli-1 in normal cell function and malignant transformation

Cited by 111 publications

References 59 publications

Deregulation of ETS1 and FLI1 contributes to the pathogenesis of diffuse large B-cell lymphoma

Deregulation of ETS1 and FLI1 contributes to the pathogenesis of diffuse large B-cell lymphoma

Utility of the immunohistochemical detection of FLI-1 expression in round cell and vascular neoplasm using a monoclonal antibody

Persistent Down-Regulation of Fli1, a Suppressor of Collagen Transcription, in Fibrotic Scleroderma Skin

Contact Info

Product

Resources

About