IRF8 (Interferon Regulatory Factor 8)

These findings suggest that the long-lived inflammatory cells may compensate for the HSC self-renewal defects, triggering systemic inflammation and driving hematopoietic malignant transformation. This paradigm provides a new understanding of hematopoietic malignancies with functional defects and exhaustion of HSCs.

In conclusion, this multicenter study suggests that most MS are of myelomonocytic/monoblastic origin, a high proportion of them are NPM1 mutated, and may lack expression of MPO and CD34. NPM1 mutation-specific antibodies should be integrated into the diagnostic panels for MS or LC, while IRF8 and PU.1 are not recommended as they cannot distinguish MS from histiocytic neoplasms.

Preclinical studies show that genetic depletion, small-molecule inhibition, or targeted degradation of FTO increases m6A on key targets, suppresses leukemic growth, and can sensitize cells to standard therapies, supporting FTO as a druggable epitranscriptomic vulnerability. This review summarizes FTO structure and function, highlights subtype-specific mechanisms in AML and ALL, and discusses emerging therapeutic strategies and translational challenges.

In vitro -generated cDC1s resemble intratumoral DC populations found in mice and humans. MHC-I and MHC-II antigen presentation by vaccine-delivered cDC1s contribute to antitumor efficacy.Coexpression of MHC-I and MHC-II on the same cDC1 enhances vaccine responses.Antitumor responses reflect the activity of vaccine and endogenous cDC1s.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries, and B-cell receptor (BCR) pathway inhibitors such as idelalisib and ibrutinib are currently established therapies for CLL. We conclude that BCR pathway inhibitors enhance AID mutational activity in CLL, but this does not appear to be directly involved in driving drug resistance. AID-targeted loci may nonetheless serve as biomarkers for monitoring genomic instability during treatment and inform further study.

This integrative multi-omics approach reveals that key molecular alterations underlie HGSOC recurrence and identifies IL7R, IRF8, PTPRC, and NSG1 as potential prognostic biomarkers and therapeutic targets. Our findings provide a foundation for targeted strategies to improve outcomes for patients with recurrent HGSOC.

Additionally, this review examines the interplay among molecular mechanisms that regulate osteoclast differentiation and activation under pathological and inflammatory conditions, elucidates their roles in osteoclast hyperactivation-related human diseases, and provides a comprehensive framework for understanding these processes. Finally, it underscores potential novel therapeutic strategies for osteoclast-related skeletal lytic diseases and highlights perspectives for future investigations.

Finally, IRF1 expression, transcription rate, and enhancer activity induced by IL-1β, or TNFα, were relatively unaffected by glucocorticoid. IRF1-dependent gene expression may therefore show insensitivity to glucocorticoid and could contribute to glucocorticoid-resistance in diseases that include severe asthma.

© 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

The degradation of IRF-8 ultimately contributes to tumor progression enhancement. Clinically, the presence of pS69 on TRIM63 is associated with tumor immunosuppression and poor prognosis among melanoma patients, highlighting its potential as a promising therapeutic target.

This sequential, cis-regulated activation appears to be the core mechanism for progressively tuning chromatin accessibility, ensuring robust lineage commitment. While its molecular basis is obscure, this dependency offers a new model for understanding genomic regulation in development.

At the loop anchor regions, IRF8 recruited CTCF to form active chromosomal structures to regulate gene transcription. These results thus identify a critical role of IRF8-dependent chromatin topology during exhausted CD8+ T cell differentiation.