Aberrant activation mechanisms of the NOTCH signaling pathway in T lymphoblastic lymphoma: mechanisms and targeted therapeutic implications

T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive non-Hodgkin lymphoma derived from precursor T cells, characterized by rapid clinical progression and a high relapse rate, with a particularly unfavorable prognosis in adult patients. Accumulating evidence indicates that the NOTCH signaling pathway plays a central oncogenic role in the initiation and progression of T-LBL. Its sustained aberrant activation is driven by multiple layers of mechanisms, including NOTCH1 gene mutations or fusions, synergistic amplification through multiple oncogenic signaling cascades, and dysregulated epigenetic control. Aberrantly activated NOTCH signaling promotes tumor cell proliferation, suppresses apoptosis, and contributes to chemotherapy resistance and disease relapse. This review focuses on the mechanisms underlying aberrant NOTCH activation in T-LBL and summarizes the principal therapeutic strategies targeting this pathway, along with their limitations, aiming to provide a framework for deeper under-standing of the molecular pathogenesis of T-LBL and for the development of more precise targeted therapies.