IRF4 mutation

Here we summarize the current understanding of the molecular pathogenesis of ATLL, focusing on recent progress made by genetic, epigenetic, and single-cell analyses. These findings not only provide a deeper understanding of the molecular pathobiology of ATLL, but also have significant implications for diagnostic and therapeutic strategies.

IRF4-C99R thoroughly modifies IRF4 function by blocking IRF4-dependent plasma cell induction, and up-regulates disease-specific genes in a non-canonical Activator Protein-1 (AP-1)-IRF-CE (AICE)-dependent manner. Our data explain how a single mutation causes a complex switch of TF specificity and gene regulation and open the perspective to specifically block the neomorphic DNA-binding activities of a mutant TF.

After removing patients with poor prognostic factors, this study aims to investigate the relationship between the DLBCL genetic landscape and the efficacy of first-line R-CHOP or R-CHOP-like regimens...According to CMap, IRF4mutpatients may benefit from lenalidomide, ibrutinib, or mitoxantrone contained regimens. Conclusions The presence of IRF4 mutation is an independent predictor of prognosis in DLBCL patients, and nonGCB subtypes in this population are significantly associated with shorter PFS. While IRF4mut GCB patients tends to have better clinical outcome.

Both lacked mutations involving IRF4 and NF-kB pathway genes that are frequently detected in large B-cell lymphoma with IRF4 rearrangement, and one case showed DLBCL-EZH2 type mutations, including KMT2D and BCL2 mutations, similar to 2 previously reported DLBCL with BCL2 and IRF4 rearrangements. Adults with FL and FL/DLBCL with BCL2 and IRF4 rearrangements display clinicopathologic and mutational features more akin to FL and DLBCL and should not be characterized as large B-cell lymphoma with IRF4 rearrangement.

The identification of specific mutations in each subgroup, which were largely consistent with previous studies, indicates that the LymphGen classifier may be valuable in individualized treatment approaches for DLBCL patients. Additionally, this study demonstrates that unclassified group ("Other") may potentially be established as a distinct subgroup.