Exploring the Anti-Leukemic Effect of the Synthetic Retinoid ST1926 on Malignant T Cells: A Comprehensive Proteomics Approach.

T-cell malignancies represent a group of complex cancers arising from T cells and include aggressive subtypes such as Adult T-cell Leukemia/Lymphoma (ATL) and T-cell Acute Lymphoblastic Leukemia (T-ALL). Patients with these aggressive subtypes still represent an unmet medical condition. The synthetic adamantyl retinoid ST1926, a potent DNA polymerase-α inhibitor, proved a promising potency in preclinical models of ATL and peripheral T-cell lymphoma. Using advanced liquid chromatography-mass spectrometry (LC-MS/MS) techniques, we explored the effects of ST1926 on global protein expression in ATL (HuT-102) and T-ALL (MOLT-4) cells. We demonstrate that ST1926 triggers differentiation and apoptosis in malignant T-cells while halting tumor progression. Evidence at the proteomics level reveals the impact of ST1926 on crucial DNA replication enzymes and cell cycle regulation, highlighting its potential to reduce leukemogenesis and promote apoptosis. Our findings underscore the potential of ST1926 as an innovative therapeutic approach to address these aggressive T-cell malignancies, providing valuable insights into developing new targeted therapies and improving the outcomes and prognosis of patients with these challenging diseases.