Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, GME office, 12902 USF Magnolia Drive, Tampa, FL 33612, USA; University of South Florida, Morsani College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA.
Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, GME office, 12902 USF Magnolia Drive, Tampa, FL 33612, USA.
Hematol Oncol Clin North Am. 2020 Apr;34(2):421-440. doi: 10.1016/j.hoc.2019.11.004. Epub 2019 Dec 12.
Mutations in TP53 are observed in ∼20% of patients with myelodysplastic syndromes (MDS), with increased frequency seen in patients with a complex karyotype and cases of therapy-related MDS. TP53 mutations represent perhaps the single greatest negative prognostic indicator in MDS. Inferior outcomes are demonstrated with all approved treatment approaches, although hypomethylating agents remain the standard frontline treatment option. Although outcomes with allogeneic hematopoietic stem cell transplant are poor, it remains the only potentially curative therapy. Novel agents are required to improve outcomes in this molecular subgroup, with therapies that directly target the mutant protein and immunotherapies demonstrating greatest potential.
TP53 基因突变可见于约 20%的骨髓增生异常综合征（MDS）患者，复杂核型和治疗相关 MDS 患者中频率更高。TP53 基因突变可能是 MDS 中唯一最重要的负性预后指标。所有已批准的治疗方法均显示预后不良，尽管去甲基化剂仍然是标准的一线治疗选择。尽管异基因造血干细胞移植的结局较差，但它仍然是唯一可能治愈的治疗方法。需要新型药物来改善这一分子亚组的预后，直接针对突变蛋白的治疗药物和免疫疗法显示出最大的潜力。
