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

Abstract

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