ERG和c-MYC调节BCR::ABL1驱动的B细胞急性淋巴细胞白血病中的关键基因网络
Kira Behrens1,2, Natalie Brajanovski3, Zhen Xu1,2
1Blood Cells and Blood Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Science advances
|March 8, 2024
概括
费城染色体阳性B细胞急性淋巴细胞白血病 (B-ALL) 依赖于ERG和c-MYC转录因子. 抑制RNA聚合酶I (POL I) 针对这些漏洞,为这种预后不佳的癌症提供新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 基因法规 基因法规
背景情况:
- 费城染色体阳性B细胞急性淋巴细胞白血病 (B-ALL) 是一种高风险的癌症,治疗选择有限.
- 融合基因驱动B-ALL的病变发生.
- 对于BCR::ABL1 B-ALL.急需新的治疗点.
研究的目的:
- 研究瘤转录因子ERG和c-MYC在BCR::ABL1 B-ALL中的作用.
- 在这种白血病中,确定由ERG和c-MYC控制的调节网络.
- 探索ERG和c-MYC调节的向途径的治疗潜力.
主要方法:
- 转录形状分析以识别高调的基因.
- 对ERG和c-MYC依赖基因表达的分析.
- 染色体免疫沉测序 (ChIP-seq) 用于绘制调控元素的地图.
- 使用RNA聚合酶I (POL I) 抑制剂抑制BCR:ABL1细胞.
主要成果:
- ERG和c-MYC是瘤转录因子,对BCR::ABL1和B-ALL至关重要.
- ERG和c-MYC协调一个监管网络,控制核糖体生物发生和代谢途径.
- 抑制POL I,这是核糖体生物发生的一个关键组成部分,有效地抑制BCR:ABL1细胞.
结论:
- 一个关键的ERG和c-MYC依赖的转录网络调节了BCR::ABL1 B-ALL中的代谢和核糖体生物发生路径.
- 针对POL I是一个有前途的治疗策略,用于BCR::ABL1 B-ALL.
- 这项研究揭示了B-ALL.在BCR::ABL1中的以前未被识别的漏洞和潜在的治疗点.
相关概念视频
02:23Abnormal 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
01:06Induced Pluripotent Stem Cells
4.1K
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...
4.1K
02:38Mitogens and the Cell Cycle
6.5K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.5K
01:33Cancer-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
00:50Anaphase Promoting Complex
2.9K
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
2.9K
01:15Differentiation of Common Myeloid Progenitor Cells
3.2K
Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
3.2K