儿科白血病型蛋白NUP98-KDM5A诱导基因组不稳定性,可能促进恶性转变
Joan Domingo-Reinés1, Rosa Montes1,2, Adrián Garcia-Moreno1
1GENYO, Centre for Genomics and Oncological Research Pfizer - University of Granada - Andalusian Regional Government, PTS, 18016, Granada, Spain.
Cell death & disease
|June 10, 2023
概括
儿科急性髓性白血病 (AML) 涉及基因融合. 这项研究表明,NUP98-KDM5A蛋白质导致儿科AML的基因组不稳定,导致疾病进展.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 儿科急性髓性白血病 (AML) 是一种罕见的癌症,具有许多基因融合.
- 目前的治疗方法加剧化疗,但50%的患者复发,面临严重的副作用.
研究的目的:
- 了解NUP98-KDM5A融合蛋白在儿科AML中的生物学影响.
- 探索新的治疗目标,以改善治疗结果.
主要方法:
- 在人类多能干细胞模型中研究了NUP98-KDM5A表达.
- 利用患者衍生的细胞系研究细胞过程.
- 分析了线粒分裂期间的DNA损伤积累和RAE1活性.
主要成果:
- 在儿科AML模型中,NUP98-KDM5A表达与基因组不稳定性有关.
- 确定了两个机制:DNA损伤积累和干扰RAE1活动.
- 融合蛋白在年轻的儿科AML患者中被发现,预后不佳.
结论:
- NUP98-KDM5A驱动了儿科AML的基因组不稳定性.
- 这种不稳定性可能有助于细胞恶性转变.
- 针对NUP98-KDM5A可能会提供一种不那么有毒的治疗策略.
相关概念视频
Abnormal Proliferation
4.6K
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...
4.6K
Induced Pluripotent Stem Cells
4.2K
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
Somatic...
4.2K
Cancer-Critical Genes I: Proto-oncogenes
9.0K
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...
9.0K
The Retinoblastoma Gene
4.1K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.1K
Nucleotide Excision Repair
3.6K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.6K
Cancer-Critical Genes II: Tumor Suppressor Genes
7.5K
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...
7.5K


