IRF4 Gene Expression on the Trail of Molecular Response: Looking at Chronic Myeloid Leukemia from Another Perspective

Abstract

Introduction Interferon regulatory factor 4 (IRF4) is a transcriptional factor with a key role in the modulation of inflammation and immune surveillance. The IRF4 gene is downregulated in Philadelphia-negative myeloproliferative neoplasms, and its expression is associated with prognosis and response to treatment. Methods We evaluated the IRF4 expression kinetics during tyrosine kinase inhibitor (TKI) treatment in a cohort of 116 chronic myeloid leukemia (CML) patients to elucidate its role in the disease course. Results A relationship between the IRF4 expression and the disease burden was observed at various disease stages. A correlation analysis between the International Scale (IS) and IRF4 values confirmed this close association. A significant increase is detected after 3 months of TKI treatment. Patients achieving early molecular response (EMR) had higher IRF4 values at both diagnosis and after 3 months of therapy as compared to those failing the EMR target. Patients achieving treatment-free remission (TFR) did not show IRF4 fluctuations during monitoring, while a decreased IRF4 expression emerged at the time of molecular relapse. Conclusion Our data seem to confirm the relevance of IRF4 in the pathogenesis of CML, suggesting a pivotal role at the disease onset and a predictive value during the CML course.

Editorial: Inflammation and blood diseases, a dog chasing its tail

“…: regulation of myeloid-derived suppressor cells (MDSCs) and polarization of anti-inflammatory M2 macrophages) was recently investigated in MPNs. IRF4 is downregulated in these disorders, and its expression is associated with the disease outcome (5,6).…”

“…The CRS history in the outcome of the UAT-ENKTL patients, the elevated PLR and CRP in the context of MDS and the IRF4 expression in MPNs can be considered new examples of "inflammatory parameters", impacting the prognosis of three different hematological diseases (Lei et al; Shi et al, 5,6).…”