FLI1 (Fli-1 Proto-Oncogene ETS Transcription Factor)

The patient received the first cycle of the chemotherapy regimen of vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide (VAC/IE) and was discharged in a stable condition. This case emphasizes the need to consider EES in the differential diagnosis of nasal masses and highlights the necessity of molecular testing for EWSR1 rearrangements to confirm the diagnosis and guide therapy. Increased awareness and reporting are vital to enhancing diagnosis and management of this rare entity.

Complete surgical excision with clear margins is essential, as incomplete excision carries a risk of local recurrence. This report highlights the importance of thorough histopathological and immunohistochemical evaluation in differentiating angiomatosis from malignant vascular tumors of the breast.

These findings underscore the need for continued collaboration to standardize diagnostic approaches across Latin America, aiming to improve treatment outcomes for ES patients.

P1/2, N=90, Recruiting, St. Jude Children's Research Hospital | Active, not recruiting --> Recruiting | N=46 --> 90

Next-Generation Sequencing (NGS) revealed EWSR1::FLI1 rearrangement in all three tested PCES cases (100%). In conclusion, the accurate diagnosis of PCES requires a comprehensive approach, integrating detailed morphologic assessment with immunohistochemical studies and potentially cytogenetics/molecular assays.

PCSK9 promoted HCC immune escape by upregulating SPP1 and PD-L1 via NOTCH3/FLI1 signaling. CRISPR ABE-mediated PCSK9 deficiency and PCSK9 inhibitor parecoxib may serve as effective strategies to inhibit HCC.

This proof-of-concept study demonstrates that DNA binding proteins with pioneering transcription factor activity, such as EWSR1::FLI1, can be relocalized on chromatin to induce expression of repressed genes. Insights herein will guide the development of future bivalent molecules that rewire DNA binding transcriptional machinery.

So, it is highly probable that a chromosomal translocation and the subsequent formation of the EWSR1-ETS fusion protein cause the genomic alterations in EwS. This indicates that targeted therapy should be directed against the CNA and LOH biology caused by the fusion protein.

These findings highlight the dual role of FLI1: tumor-intrinsic FLI1 promotes proliferation and invasion, whereas its transcriptional regulation in tumor and endothelial compartments likely reflects LSD1 dependence. Collectively, our results support a mechanistic model in which LSD1-FLI1 crosstalk is involved in immune and stromal remodeling, positioning FLI1 as both a marker of tumor aggressiveness and a potential predictor of response to epigenetic therapies in breast cancer.

This reagent will provide the research community with valuable tools for further biochemical and genomic interrogation of the oncogenic activity of EWS::FLI1 in ES.

EWSR1 could be a powerful prognostic indicator for clinical strategy selection in AML. The prediction model may effectively predict the OS of non-APL AML.

The noncompetitive lysine-specific demethylase 1 (LSD1) inhibitors SP-2509 and SP-2577 are N'-(1-phenylethylidene)-benzohydrazides that display potent activity in Ewing sarcoma. This unique activity is instead associated with the N'-(2-hydroxybenzylidene)-benzohydrazide core and destabilization of Fe-S proteins. These findings reveal a novel mechanism of action for this class of compounds and raise additional questions regarding how EWSR1::FLI1 transcriptional regulation is linked to Fe-S biogenesis, the precise mechanisms of cell death, the biological features of susceptible cancer cells, and strategies for clinical translation.