Mirgayazova Regina, Khadiullina Raniya, Gilyazova Elvina, Davletshin Damir, Ganeeva Irina, Zmievskaya Ekaterina, Chasov Vitaly, Valiullina Aygul, Bulatov Emil
Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.
Mol Biol Res Commun. 2025;14(3):179-198. doi: 10.22099/mbrc.2025.51477.2054.
The gene encodes the tumor suppressor protein p53, which plays a critical role in genomic stability and cell cycle regulation. mutations are prevalent in approximately half of all human malignancies and are associated with poor clinical outcomes, including increased genomic instability, chemoresistance, and reduced survival rates. However, the prognostic and predictive value of status remains inconsistent across cancer types. Chronic lymphocytic leukemia (CLL) stands out as a disease where alterations have a well-established clinical significance, influencing treatment decisions and patient prognosis. In CLL, mutations and 17p deletions are strongly correlated with advanced disease stages, resistance to chemo-immunotherapy, and poor overall survival. The European Research Initiative for CLL (ERIC) has recognized status as a crucial prognostic biomarker, advocating for its routine assessment in clinical practice. Given the limitations of traditional therapies in -mutated CLL, novel targeted therapies, including BCL2 and BTK inhibitors, as well as CAR-T cell therapy, are being explored to improve patient outcomes. This review provides an in-depth analysis of the evolving role of status in CLL, with a particular focus on emerging therapeutic strategies, including CAR-T cell therapy, and their potential to overcome -driven treatment resistance.
该基因编码肿瘤抑制蛋白p53，其在基因组稳定性和细胞周期调控中起关键作用。p53突变在大约一半的人类恶性肿瘤中普遍存在，并且与不良临床结果相关，包括基因组不稳定性增加、化疗耐药性和生存率降低。然而，p53状态的预后和预测价值在不同癌症类型中仍不一致。慢性淋巴细胞白血病（CLL）作为一种疾病脱颖而出，其中p53改变具有明确的临床意义，影响治疗决策和患者预后。在CLL中，p53突变和17p缺失与疾病晚期、对化疗免疫治疗的耐药性以及较差的总生存率密切相关。欧洲慢性淋巴细胞白血病研究倡议（ERIC）已将p53状态视为一种关键的预后生物标志物，主张在临床实践中对其进行常规评估。鉴于传统疗法在p53突变型CLL中的局限性，正在探索包括BCL2和BTK抑制剂以及CAR-T细胞疗法在内的新型靶向疗法以改善患者预后。本综述对p53状态在CLL中不断演变的作用进行了深入分析，特别关注新兴治疗策略，包括CAR-T细胞疗法，以及它们克服p53驱动的治疗耐药性的潜力。
