APEX1多态性影响急性髓性白血病风险,其表达涉及细胞增殖和分化
Nanami Gotoh1, Tsukasa Oda2, Yuya Kitamura1
1Department of Laboratory Science, Graduate School of Health Sciences, Gunma University, Maebashi, Japan.
International journal of laboratory hematology
|November 13, 2024
概括
基因切除修复 (BER) 基因的遗传变异,特别是APEX1,与急性髓性白血病 (AML) 风险有关. APEX1在AML细胞分化和增殖中发挥着关键作用.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- DNA修复基因多态性因其在癌症易感性中的作用而越来越被认可.
- 基因切除修复 (BER) 途径基因对于保持基因组稳定性至关重要.
- 在急性髓性白血病 (AML) 中研究BER基因多态性可以阐明疾病的发病因子.
研究的目的:
- 检查基切除修复 (BER) 基因多态性与患急性髓性白血病 (AML) 的风险之间的关联.
- 研究APEX1基因表达在AML病变发生中的作用,包括细胞分化和增殖.
主要方法:
- 在106名AML患者和191名健康对照中对四个BER基因 (APEX1,MUTYH,OGG1,XRCC1) 进行基因定型.
- 从AML患者和对照组的骨髓样本中分析APEX1表达水平.
- 功能性检测包括AML细胞系中的APEX1敲除和CD34+细胞百分比分析.
主要成果:
- 在衰退型和共主导型模型下,APEX1-656 T>G多态性与增加的AML风险显著相关.
- 与对照组相比,AML骨髓中的APEX1表达显著增加.
- APEX1 knockdown 降低了AML细胞增殖,其表达水平与CD34+细胞百分比相关.
结论:
- APEX1基因多态性代表了急性髓性白血病的潜在危险因素.
- APEX1在调节AML细胞的分化和扩散方面发挥着至关重要的作用.
- 准APEX1可能为AML治疗提供治疗策略.
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
Induced Pluripotent Stem Cells
3.9K
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...
3.9K
Combination Therapies and Personalized Medicine
4.9K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
4.9K
Cancer-Critical Genes I: Proto-oncogenes
8.7K
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...
8.7K
RNA Splicing
56.0K
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
56.0K
The Intrinsic Apoptotic Pathway
6.4K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.4K


