KMT2A (MLL1) encodes a histone H3K4 methyltransferase critical for epigenetic activation, but its role in mature T-cell lymphomas (PTCL) remains unclear. We re-analyzed the public dataset GSE58445 (n = 193) to define the transcriptional and clinical correlates of KMT2A expression. Probe-level data were re-annotated to gene symbols, and tumors were stratified as KMT2A-high or KMT2A-low by median expression. Differential expression was assessed with limma, and pathway enrichment with gene-set enrichment analysis (GO/KEGG). Survival time and status were extracted from sample metadata. KMT2A-high tumors displayed hundreds of differentially expressed genes (false-discovery rate < 10⁻¹²), enriched for ATP-dependent chromatin-remodeling, mRNA catabolic/surveillance, autophagy-lysosomal, and DNA-repair pathways, consistent with an epigenetically adaptive stress-response phenotype. KMT2A expression did not segregate with GATA3-like or TBX21-like molecular subclasses (p ≈ 0.05) and correlated only weakly with TBX21 (r = –0.12, p = 0.09), suggesting a lineage-independent chromatin axis. Overall survival did not differ between KMT2A-high and KMT2A-low groups (log-rank p = 0.81). MEN1 transcript levels, encoding menin, were unchanged (logFC ≈ 0.01, adj p = 0.9), but the KMT2A-high signature paralleled menin-KMT2A–dependent transcriptional programs seen in leukemia, including chromatin-remodeling and RNA-turnover networks. These data identify a KMT2A-associated epigenetic state in PTCL that may confer transcriptional plasticity without direct KMT2A rearrangements. We propose that this subset may exhibit functional menin–KMT2A dependency analogous to that therapeutically targeted by menin–KMT2A interaction inhibitors (e.g., revumenib), supporting pre-clinical testing of menin–KMT2A blockade alone or with histone-modifying or T-cell-directed therapies.
