Disease relevance of Flii

• In the multistage erythroleukemias induced by the various strains of Friend leukemia virus, the analysis of proviral-integration events has led to the identification of two genes, Fli-1 and Spi-1, both novel members of the ets oncogene family of transcription factors [1].
• Objectives: Friend leukemia integration-1 (Fli-1), a member of the Ets gene family of transcription factors, has been demonstrated to be a target of a leukaemia inducing virus in mice, and is known to be part of a fusion gene in Ewings' sarcoma in humans [2].
• Proliferation of atypical megakaryocytes is a predominant histopathological feature in Philadelphia chromosome negative chronic myeloproliferative disorders (Ph(-) CMPD) and a potential aberrant expression of Fli-1 has not been investigated so far [2].

High impact information on Flii

• Cultured homozygous Fliih mutant blastocysts hatch, attach, and form an outgrowing trophoblast cell layer, but egg cylinder formation fails and the embryos degenerate [3].
• Fliih, a gelsolin-related cytoskeletal regulator essential for early mammalian embryonic development [3].
• We have disrupted the mouse homologue Fliih by homologous recombination in embryonic stem cells [3].
• The overall stronger labelling for Fli-1 in megakaryocytes in Ph(-) CMPD most likely reflects the degree of polyploidisation but aberrant activation of nuclear target genes can not be excluded [2].
• Conclusion: Fli-1 is rather constitutively expressed by bone marrow cells in Ph(-) CMPD independent of the underlying JAK2 status [2].

Biological context of Flii

• We have cloned Fliih, the corresponding chromosomal gene from the mouse, and determined its nucleotide sequence (15.6 kb) [4].
• Like the human gene, Fliih has 29 introns, compared with 13 in C. elegans and 3 in D. melanogaster [4].
• Fluorescence in situ hybridization was used to map Fliih to Chromosome 11B [4].
• Fliih lies adjacent to Llglh, the mouse homologue of the D. melanogaster tumor suppressor gene lethal(2) giant larvae [4].
• Fli-1 protein expression by myeloid progenitors was considerably heterogenous in Ph(-) CMPD independent of an underlying JAK2 (V617F) mutation and without notable differences to non-neoplastic haematopoiesis [2].

Anatomical context of Flii

• Wild-type Fli-1 is involved in lineage commitment of megakaryocytes and myeloid progenitors through induction of Janus kinases (JAKs) following ligand binding to cytokine and growth factor receptors [2].

Analytical, diagnostic and therapeutic context of Flii

• Results from immunoprecipitation and a two-hybrid assay further indicated that Fliih directly interfered with the formation of the TLR4-MyD88 signaling complex [5].
• By immunohistochemistry, Fli-1 protein could be detected in nuclei of atypical megakaryocytes in Ph(-) CMPD and, less accentuated, in non-neoplastic megakaryocytes [2].

References