In patients with TP53 mutations, these alterations may lead to novel, selective vulnerabilities, creating opportunities for therapeutic targeting of TP53 mutant AML. The mutational status of TP53 therefore poses challenges and opportunities in terms of advancing effective treatment strategies in AML.

2021年10月5日 · Mutation of the tumor suppressor gene, TP53, is associated with abysmal survival outcomes in acute myeloid leukemia (AML). Although it is the most commonly mutated gene in cancer, its occurrence is observed in only 5-10% of de novo AML, and in 30% of therapy related AML (t-AML).

The most common mutations in acute myeloid leukemia (AML) occur in the DNA-binding domain of p53. TP53 mutations are associated with a very poor prognosis and define a unique disease subgroup within AML. TP53-mutated AML often shows limited response to conventional chemotherapy and even allogeneic hematopoietic stem cell transplantation.

2024年5月20日 · TP53 mutations are found in 5%-10% of de novo myelodysplastic syndrome (MDS) and AML cases. By contrast, in therapy related MDS and AML, mutations in TP53 are found in up to 30%-40% of patients. The majority of inactivating mutations observed in MDS and AML are missense mutations localized in a few prevalent hotspots.

2016年11月25日 · TP53 mutations are associated with the lowest survival rates in acute myeloid leukemia (AML). In addition to mutations, loss of p53 function can arise via aberrant expression of proteins that...

2023年2月18日 · TP53 mutated (m) acute myeloid leukemia (AML) is associated with high relapse rate and poor overall survival (OS) [1, 2, 3]. Response to cytotoxic chemotherapy is highly dependent on the...

2024年11月19日 · TP53 mutations are found in approximately 5% to 10% of patients with de novo acute myeloid leukemia (AML), more frequently observed in elderly patients and those with therapy-related AML....

TP53 gene mutations occurring in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are associated with high-risk karyotypes including 17p abnormalities, monosomal and complex cytogenetics. TP53 mutations in these disorders portend rapid disease progression and resistance …

2024年12月26日 · 《Blood Cancer Journal》近日发表综述，全面概述了 AML 中的 TP53 突变、基于等位基因负荷的结局、临床意义、治疗挑战和改善长期预后的策略。 TP53 基因也称为基因组守护者，是位于染色体17p13.1上的肿瘤抑制基因，是人类肿瘤中最常见的突变基因，它编码393个氨基酸的磷蛋白 (p53)，p53是细胞周期调控、DNA修复、细胞凋亡和代谢途径的关键转录因子。 TP53突变在实体瘤中更常见，在急性髓系白血病 (AML) 中约为10%-15%；此外据报 …

2025年3月2日 · 在难治性复发性AML和CML患者中，RG7112可触发wtp53激活，并提高许多p53靶基因的表达，在许多患者中观察到RG7112的抗白血病活性。 然而，需要大剂量的RG7112才能达到疗效，导致不良事件发生，如胃肠道不耐受和血小板生成抑制。