Acute Myeloid Leukemia (AML) with KMT2A rearrangements, referred to as KMT2A-rearranged AML (KMT2Ar-AML), has been identified as particularly aggressive, often leading to rapid disease progression and poor patient outcomes. Recent research has shed new light on the role of lactylation—an epigenetic modification—illustrated as having significant impacts on gene expression within this subtype of leukemia.
This novel study investigates the influence of lactylation on KMT2Ar-AML, identifying key lactylation-dependent differentially expressed genes (DEGs) valuable for prognosis and treatment strategies. Historical background reveals the alterations on chromosome 11q23 linked to KMT2A rearrangements occur in about 5-10% of pediatric cases and serve as adverse prognostic indicators.
Using high-throughput microarray platforms, researchers analyzed 70 KMT2Ar-AML samples alongside 52 control samples, highlighting substantial molecular differences illustrated through comparative analyses. A total of 646 DEGs were determined, with 360 showing upregulation and 286 downregulation, encompassing significant molecular variances intrinsic to KMT2Ar-AML.
The study’s findings focused on lactylation-related genes, defining twelve notable lactylation-dependent DEGs. Utilizing advanced machine learning strategies, six core genes emerged as pivotal: Profilin 1 (PFN1), S100A6, Carbonyl Reductase 1 (CBR1), Lactate Dehydrogenase B (LDHB), Galectin 1 (LGALS1), and Peroxiredoxin 1 (PRDX1). Each possesses considerable promise for improving diagnostic accuracy and elucidates pathways linked to disease progress.
Particularly noteworthy were the predictive values established through receiver operating characteristic (ROC) curve analyses demonstrating significant AUC values—suggesting these genes might serve as biomarkers to differentiate KMT2Ar-AML from other types of leukemia.
Monitoring immune cell infiltration revealed distinct profiles within KMT2Ar-AML, with correlations between certain LactoKey genes and immune populations. The presence of immune cell types, particularly myeloid-derived suppressor cells (MDSCs), symbolized the dual nature of immunity and disease progression interplay.
The research propels lactylation to the forefront of cancer treatment explorations. Beyond identifying these key genes, the study discussed potential therapeutic options, such as PI3K inhibitors, illustrating how modulation of lactylation might open doors to enhanced treatment protocols.
Future clinical validation and explorations will be instrumental, potentially broadening therapeutic horizons. Integrative strategies centered around lactylation-related pathways may yield promising results, emphasizing the need for continued research to refine treatment opportunities and outcomes for patients facing KMT2A-rearranged AML.