Exploring the oncogenetic landscape of T-LBL to identify candidate markers for disease progression and relapse. Frequent alterations found in T-LBL lead to uncontrolled activation of oncogenetic pathways, including NOTCH1, JAK-STAT, and PI3K/Akt. Additionally, deletion of cell-cycle repressors CDKN2A and CDKN2B or LOH6q elicit cell proliferation and suppress apoptosis. Mutations of transcription factors and epigenetic regulators reshape cell identity and sustain malignant cell expansion and disease progression. Alterations frequencies are indicated for the main events. Integrative approaches combining next-generation DNA sequencing, epigenomics, and transcriptomics have to be engaged. Such investigations are required to determine the oncogenetic drivers of T-LBL and candidate markers of clinical outcomes, notably the treatment response and relapse risk. LOH6q, loss of heterozygosity at chromosome 6q.