低负荷TP53突变代表了CLL频繁发生的遗传事件,增加了治疗开始的风险
Tamás László1, Lili Kotmayer1, Viktória Fésüs1,2
1HCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
The journal of pathology. Clinical research
|November 21, 2023
概括
慢性淋巴细胞白血病 (CLL) 中的低负荷TP53突变很常见,并且与早期的治疗需求有关. 重新定义TP53变异报告率低于10%对于患者护理至关重要.
科学领域:
- 血液学 血液学 血液学
- 在瘤学瘤学.
- 遗传学 是一个遗传学.
背景情况:
- 慢性淋巴细胞白血病 (CLL) 中的TP53异常表明化学抵抗性,并禁忌标准化疗免疫疗法.
- 通过下一代测序 (NGS) 检测到的低负荷TP53突变 (变异性基因频率<10%) 的临床意义仍在争论中.
研究的目的:
- 研究TP53突变的克隆结构和临床影响,包括低负荷变异,在一个大型的真实世界CLL队列中.
- 用敏感的NGS分析评估低负荷TP53突变的频率和临床相关性.
主要方法:
- 对901名患有CLL的患者进行了基于NGS的敏感突变分析.
- 分析了TP53突变负担 (高与低) 和克隆架构.
- 在患有野生型TP53,高负荷和低负荷TP53突变的患者之间比较了到第一次治疗的时间.
主要成果:
- 在17.5%的患者 (158/901) 中发现了TP53突变,其中52%被归类为低负担.
- 在显著比例的突变病例中,发现了低负荷TP53突变,特别是作为鞋底变异.
- 与野生型TP53.3患者相比,患有低负荷TP53突变的患者的首次治疗时间显著缩短.
结论:
- 低负荷TP53突变在CLL中很常见,并影响临床结果,需要更早地开始治疗.
- 这些发现支持重新定义TP53变种报告门,使其在常规诊断中低于10%.
- 准确识别低负荷TP53突变对于个性化的CLL治疗策略至关重要.
相关概念视频
Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
Cancer-Critical Genes II: Tumor Suppressor Genes
7.4K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
7.4K
Cancers Originate from Somatic Mutations in a Single Cell
12.0K
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
12.0K
Non-LTR Retrotransposons
11.5K
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
11.5K
Cancer-Critical Genes I: Proto-oncogenes
8.9K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
8.9K
Targeted Cancer Therapies
7.7K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
7.7K


