Kojima Kensuke
Department of Hematology, Kochi Medical School, Kochi University.
Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center.
Rinsho Ketsueki. 2023;64(9):955-961. doi: 10.11406/rinketsu.64.955.
Anthracycline- and cytarabine-based intensive combination chemotherapies are considered the backbone therapy for patients with acute myeloid leukemia (AML). Although chemotherapy leads to long-term remission and cures many patients with AML, it can induce DNA damage/stress due to acute/chronic toxicities, acquired resistance, relapse, and therapy-related malignancies. Introduction of molecularly targeted agents with less systemic toxicities has considerably improved the scope of treatment, particularly in elderly and frail patients. However, outcomes of TP53-mutated myelodysplastic syndrome (MDS) and AML, a distinct group of myeloid disorders, have not improved irrespective of the treatment used (median overall survival, 5-10 months). In this review, we discuss the biological and clinical significance of TP53 mutations in malignancies, while particularly focusing on MDS/AML, and emerging therapies for TP53-mutated MDS/AML. Rationally designed novel treatment strategies are expected to improve the clinical outcomes of TP53-mutated MDS/AML.
基于蒽环类药物和阿糖胞苷的强化联合化疗被认为是急性髓系白血病（AML）患者的主要治疗方法。尽管化疗可导致长期缓解并治愈许多AML患者，但由于急性/慢性毒性、获得性耐药、复发及治疗相关恶性肿瘤，它可诱导DNA损伤/应激。引入全身毒性较小的分子靶向药物已显著改善了治疗范围，尤其是在老年和体弱患者中。然而，无论采用何种治疗方法，TP53突变的骨髓增生异常综合征（MDS）和AML（一种独特的髓系疾病组）的预后均未改善（中位总生存期为5 - 10个月）。在本综述中，我们讨论TP53突变在恶性肿瘤中的生物学和临床意义，尤其关注MDS/AML，以及针对TP53突变的MDS/AML的新兴疗法。合理设计的新型治疗策略有望改善TP53突变的MDS/AML的临床结局。
