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== Clinical significance ==
== Clinical significance ==


In addition to Friend erythroleukemia, proviral integration at the fli-1 locus also occurs in leukemias induced by the 10A1, Graffi, and Cas-Br-E viruses. Fli-1 aberrant expression is also associated with chromosomal abnormalities in humans. In pediatric [[Ewing’s sarcoma]] a chromosomal translocation generates a fusion of the 5’ transactivation domain of [[EWSR1]] (also known as EWS) with the 3’ Ets domain of Fli-1. The resulting fusion oncoprotein, EWS/Fli-1, acts as an aberrant transcriptional activator.<ref name="pmid7503813">{{cite journal |vauthors=Ohno T, Rao VN, Reddy ES | title = EWS/Fli-1 chimeric protein is a transcriptional activator | journal = Cancer Res. | volume = 53 | issue = 24 | pages = 5859–63 |date=December 1993 | pmid = 7503813 | doi = }}</ref> with strong transforming capabilities. The importance of Fli-1 in the development of human leukemia, such as acute myelogenous leukemia ([[acute myelogenous leukemia|AML]]), has been demonstrated in studies of translocation involving the [[ETV6|Tel]] transcription factor, which interacts with Fli-1 through protein-protein interactions. A recent study has demonstrated high levels of Fli-1 expression in several benign and malignant neoplasms using immunohistochemistry.{{citation needed|date=December 2010}}
In addition to Friend erythroleukemia, proviral integration at the fli-1 locus also occurs in leukemias induced by the 10A1, Graffi, and Cas-Br-E viruses. Fli-1 aberrant expression is also associated with chromosomal abnormalities in humans. In pediatric [[Ewing’s sarcoma]] a chromosomal translocation generates a fusion of the 5’ transactivation domain of [[EWSR1]] (also known as EWS) with the 3’ Ets domain of Fli-1. The resulting fusion oncoprotein, EWS/Fli-1, acts as an aberrant transcriptional activator.<ref name="pmid7503813">{{cite journal |vauthors=Ohno T, Rao VN, Reddy ES | title = EWS/Fli-1 chimeric protein is a transcriptional activator | journal = Cancer Res. | volume = 53 | issue = 24 | pages = 5859–63 |date=December 1993 | pmid = 7503813 | doi = }}</ref> with strong transforming capabilities. EWS/Fli-1 may steer clinically important genes via interaction with enhnacer-like GGAA-microsatellites.<ref>{{Cite journal|last=Musa|first=Julian|last2=Cidre-Aranaz|first2=Florencia|last3=Aynaud|first3=Marie-Ming|last4=Orth|first4=Martin|last5=Mirabeau|first5=Olivier|last6=Varon|first6=Mor|last7=Grossetete|first7=Sandrine|last8=Surdez|first8=Didier|last9=et al.|date=2018-12-27|title=Cooperation of dominant oncogenes with regulatory germline variants shapes clinical outcomes in childhood cancer|url=https://www.biorxiv.org/content/early/2018/12/27/506659|journal=bioRxiv|language=en|volume=|pages=506659|doi=10.1101/506659|via=}}</ref> The importance of Fli-1 in the development of human leukemia, such as acute myelogenous leukemia ([[acute myelogenous leukemia|AML]]), has been demonstrated in studies of translocation involving the [[ETV6|Tel]] transcription factor, which interacts with Fli-1 through protein-protein interactions. A recent study has demonstrated high levels of Fli-1 expression in several benign and malignant neoplasms using immunohistochemistry.{{citation needed|date=December 2010}}


A possible association with [[Paris-Trousseau syndrome]] has been suggested.<ref name="pmid15232614">{{cite journal |vauthors=Raslova H, Komura E, Le Couédic JP, Larbret F, Debili N, Feunteun J, Danos O, Albagli O, Vainchenker W, Favier R | title = FLI1 monoallelic expression combined with its hemizygous loss underlies Paris-Trousseau/Jacobsen thrombopenia | journal = J. Clin. Invest. | volume = 114 | issue = 1 | pages = 77–84 |date=July 2004 | pmid = 15232614 | pmc = 437972 | doi = 10.1172/JCI21197 }}</ref>
A possible association with [[Paris-Trousseau syndrome]] has been suggested.<ref name="pmid15232614">{{cite journal |vauthors=Raslova H, Komura E, Le Couédic JP, Larbret F, Debili N, Feunteun J, Danos O, Albagli O, Vainchenker W, Favier R | title = FLI1 monoallelic expression combined with its hemizygous loss underlies Paris-Trousseau/Jacobsen thrombopenia | journal = J. Clin. Invest. | volume = 114 | issue = 1 | pages = 77–84 |date=July 2004 | pmid = 15232614 | pmc = 437972 | doi = 10.1172/JCI21197 }}</ref>

Latest revision as of 20:25, 27 December 2018

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Friend leukemia integration 1 transcription factor (FLI1), also known as transcription factor ERGB, is a protein that in humans is encoded by the FLI1 gene, which is a proto-oncogene.[1][2][3]

Function

Fli-1 is a member of the ETS transcription factor family that was first identified in erythroleukemias induced by Friend Murine Leukemia Virus (F-MuLV). Fli-1 is activated through retroviral insertional mutagenesis in 90% of F-MuLV-induced erythroleukemias. The constitutive activation of fli-1 in erythroblasts leads to a dramatic shift in the Epo/Epo-R signal transduction pathway, blocking erythroid differentiation, activating the Ras pathway, and resulting in massive Epo-independent proliferation of erythroblasts. These results suggest that Fli-1 overexpression in erythroblasts alters their responsiveness to Epo and triggers abnormal proliferation by switching the signaling event(s) associated with terminal differentiation to proliferation.[citation needed]

Clinical significance

In addition to Friend erythroleukemia, proviral integration at the fli-1 locus also occurs in leukemias induced by the 10A1, Graffi, and Cas-Br-E viruses. Fli-1 aberrant expression is also associated with chromosomal abnormalities in humans. In pediatric Ewing’s sarcoma a chromosomal translocation generates a fusion of the 5’ transactivation domain of EWSR1 (also known as EWS) with the 3’ Ets domain of Fli-1. The resulting fusion oncoprotein, EWS/Fli-1, acts as an aberrant transcriptional activator.[4] with strong transforming capabilities. EWS/Fli-1 may steer clinically important genes via interaction with enhnacer-like GGAA-microsatellites.[5] The importance of Fli-1 in the development of human leukemia, such as acute myelogenous leukemia (AML), has been demonstrated in studies of translocation involving the Tel transcription factor, which interacts with Fli-1 through protein-protein interactions. A recent study has demonstrated high levels of Fli-1 expression in several benign and malignant neoplasms using immunohistochemistry.[citation needed]

A possible association with Paris-Trousseau syndrome has been suggested.[6]

References

  1. ↑ Baud V, Lipinski M, Rassart E, Poliquin L, Bergeron D (September 1991). "The human homolog of the mouse common viral integration region, FLI1, maps to 11q23-q24". Genomics. 11 (1): 223–4. doi:10.1016/0888-7543(91)90124-W. PMID 1765382.
  2. ↑ Prasad DD, Rao VN, Reddy ES (October 1992). "Structure and expression of human Fli-1 gene". Cancer Research. 52 (20): 5833–7. PMID 1394211.
  3. ↑ Rao VN, Ohno T, Prasad DD, Bhattacharya G, Reddy ES (August 1993). "Analysis of the DNA-binding and transcriptional activation functions of human Fli-1 protein". Oncogene. 8 (8): 2167–73. PMID 8336942.
  4. ↑ Ohno T, Rao VN, Reddy ES (December 1993). "EWS/Fli-1 chimeric protein is a transcriptional activator". Cancer Res. 53 (24): 5859–63. PMID 7503813.
  5. ↑ Musa, Julian; Cidre-Aranaz, Florencia; Aynaud, Marie-Ming; Orth, Martin; Mirabeau, Olivier; Varon, Mor; Grossetete, Sandrine; Surdez, Didier; et al. (2018-12-27). "Cooperation of dominant oncogenes with regulatory germline variants shapes clinical outcomes in childhood cancer". bioRxiv: 506659. doi:10.1101/506659.
  6. ↑ Raslova H, Komura E, Le Couédic JP, Larbret F, Debili N, Feunteun J, Danos O, Albagli O, Vainchenker W, Favier R (July 2004). "FLI1 monoallelic expression combined with its hemizygous loss underlies Paris-Trousseau/Jacobsen thrombopenia". J. Clin. Invest. 114 (1): 77–84. doi:10.1172/JCI21197. PMC 437972. PMID 15232614.

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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