表观遗传失调的NOTCH-Delta-HES信号级联可以作为急性淋巴细胞白血病的亚型分类器
Syeda Saliah Hussan1, Muhammad Shrafat Ali1, Mishal Fatima1
1Biopharmaceuticals and Biomarkers Discovery Lab., School of Biochemistry and Biotechnology, University of the Punjab, Lahore, 54590, Pakistan.
Annals of hematology
|November 3, 2023
概括
在NOTCH-Delta-HES路径.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- NOTCH-Delta-HES信号级联在癌症中表现出双重作用,同时作为瘤抑制剂和瘤基因.
- 它在T细胞和B细胞中的复杂行为表明了白血病分类的潜力.
研究的目的:
- 研究NOTCH-Delta-HES途径作为急性淋巴细胞白血病 (ALL) 的诊断生物标志物和亚型分类器的潜力.
- 在小儿ALL患者的NOTCH级联中分析基因表达和DNA甲基化模式.
主要方法:
- 定量PCR (qPCR) 用于分析骨髓 (BM) 和血 (BP) 中七个NOTCH级联基因的表达.
- 甲基化特异定量甲基化特异PCR (qMSP) 和二硫酸安普利康序列测序,以评估促进体DNA甲基化状态.
- 接收器操作特征 (ROC) 曲线分析和卡普兰-梅尔生存分析用于诊断和预后评估.
主要成果:
- 在所有ALL患者中观察到JAG1,DLL1,HES-2,HES-4和HES-5的高甲基化.
- NOTCH3高甲基化是特有的前BALL,而DLL4高甲基化是特有的前TALL.
- 异常的DNA甲基化与减少的基因表达相关,在实现完全缓解后正常化.
- 在BM和BP的表观遗传特征显示了可比的诊断潜力.
结论:
- NOTCH-Delta-HES表观遗传特征表明,它有可能成为急性淋巴细胞白血病的亚型分类器.
- 这一途径可以用于ALL的最小侵入性诊断和预后.
- 这些发现支持在ALL亚型中NOTCH途径表观遗传变化的临床适用性.
相关概念视频
03:14Notch Signaling Pathway
4.3K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.3K
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.1K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.1K
01:21Lineage Commitment
3.0K
Commitment is the process whereby stem cells:
3.0K
02:33Hedgehog Signaling Pathway
7.4K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.4K
01:20The JAK-STAT Signaling Pathway
8.9K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.9K