Goli Mona, Sandilya Vishal, Ghandour Botheina, Hajj Hiba El, Kobeissy Firas, Darwiche Nadine, Mechref Yehia
Chemistry and Biochemistry Department, Texas Tech University, Lubbock, TX 79409, USA.
Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut 1107 2020, Lebanon.
Int J Mol Sci. 2025 May 13;26(10):4651. doi: 10.3390/ijms26104651.
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.
T细胞恶性肿瘤是一组源于T细胞的复杂癌症，包括侵袭性亚型，如成人T细胞白血病/淋巴瘤（ATL）和T细胞急性淋巴细胞白血病（T-ALL）。患有这些侵袭性亚型的患者仍然面临未得到满足的医疗需求。合成金刚烷基视黄酸ST1926是一种有效的DNA聚合酶α抑制剂，在ATL和外周T细胞淋巴瘤的临床前模型中显示出有前景的效力。使用先进的液相色谱-质谱联用（LC-MS/MS）技术，我们探索了ST1926对ATL（HuT-102）和T-ALL（MOLT-4）细胞中整体蛋白质表达的影响。我们证明，ST1926在使肿瘤进展停滞的同时，能触发恶性T细胞的分化和凋亡。蛋白质组学水平的证据揭示了ST1926对关键DNA复制酶和细胞周期调控的影响，突出了其减少白血病发生和促进凋亡的潜力。我们的研究结果强调了ST1926作为一种创新治疗方法来应对这些侵袭性T细胞恶性肿瘤的潜力，为开发新的靶向治疗以及改善患有这些具有挑战性疾病的患者的治疗结果和预后提供了有价值的见解。
