Abstract：
BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy characterized by uncontrolled proliferation and impaired differentiation of myeloid cells in the bone marrow. The tumor suppressor gene TP53 plays a crucial role in maintaining genomic integrity and preventing the development of cancer. TP53 mutations are frequently observed in AML (∼10% of patients) and are associated with aggressive disease behavior, resistance to therapy, and poor prognosis.
CONCLUSIONS: Recent changes in classification of TP53-mutated myelodysplastic syndrome (MDS) have occurred related to the allelic status of TP53 and more importantly to harmonize MDS/AML patients as a homogeneous hematological malignancy. Current treatment regimens involve hypomethylating agents +/- venetoclax or intensive chemotherapy although unfortunately independent of treatment regimen the overall survival (OS) of this patient cohort is around 6 months with poor long-term outcomes after allogeneic stem-cell transplantation. Recent developments geared toward the treatment of TP53-mutated MDS/AML have focused on immunotherapies.
CONCLUSIONS: Notably, there is optimism surrounding these new therapies that could provide breakthroughs with improving outcomes either as monotherapy or combined with established nonimmune therapies. This paper aims to provide an overview of TP53-mutated MDS/AML, including the underlying mechanisms, clinical implications, and emerging therapeutic strategies targeting this hematologic malignancy.
CONCLUSIONS: Recent changes in classification of TP53-mutated myelodysplastic syndrome (MDS) have occurred related to the allelic status of TP53 and more importantly to harmonize MDS/AML patients as a homogeneous hematological malignancy. Current treatment regimens involve hypomethylating agents +/- venetoclax or intensive chemotherapy although unfortunately independent of treatment regimen the overall survival (OS) of this patient cohort is around 6 months with poor long-term outcomes after allogeneic stem-cell transplantation. Recent developments geared toward the treatment of TP53-mutated MDS/AML have focused on immunotherapies.
CONCLUSIONS: Notably, there is optimism surrounding these new therapies that could provide breakthroughs with improving outcomes either as monotherapy or combined with established nonimmune therapies. This paper aims to provide an overview of TP53-mutated MDS/AML, including the underlying mechanisms, clinical implications, and emerging therapeutic strategies targeting this hematologic malignancy.
摘要：
背景技术急性髓系白血病(AML)是一种异质性血液恶性肿瘤,其特征在于骨髓中的骨髓细胞不受控制的增殖和受损的分化。抑癌基因TP53在维持基因组完整性和预防癌症发展中起着至关重要的作用。在AML中经常观察到TP53突变（约10％的患者），并且与侵袭性疾病行为有关。抵抗治疗,预后不良。摘要TP53突变的骨髓增生异常综合征（MDS）的最新分类变化与TP53的等位基因状态有关，更重要的是协调MDS/AML患者作为同质血液恶性肿瘤。目前的治疗方案涉及低甲基化剂+/-维奈托克或强化化疗，尽管不幸的是，与治疗方案无关，该患者队列的总生存期（OS）约为6个月，异基因干细胞移植后的长期预后较差。针对TP53突变的MDS/AML的治疗的最新发展集中在免疫疗法上。关键信息值得注意的是,人们对这些新疗法持乐观态度，这些新疗法可以作为单一疗法或与已建立的非免疫疗法相结合，在改善结局方面提供突破。本文旨在概述TP53突变的MDS/AML，包括潜在的机制，临床意义，以及针对这种恶性血液病的新兴治疗策略。
