线粒体功能障碍在成人T细胞急性淋巴细胞白血病中促进药物耐药性
Shanshan Guo1,2,3, Ekaterina Bourova-Flin2,3, Sophie Rousseaux2,3
1Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Journal of translational medicine
|May 14, 2025
概括
在T细胞急性淋巴细胞白血病 (T-ALL) 中,线粒体活性降低通过脂质积累激活ABCB1,从而驱动多药性耐药性. 向脂质生成可以克服T-ALL患者的化疗耐药性.
科学领域:
- 血液学 血液学 血液学
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- T细胞急性淋巴细胞白血病 (T-ALL) 是一种具有不良预后的侵袭性癌症.
- 线粒体活性下降与T-ALL攻击性相关,但治疗耐药性的机制尚不清楚.
研究的目的:
- 调查线粒体活动减少与T-ALL中药物耐药性之间的联系.
- 阐明推动T-ALL.治疗耐药性的分子机制.
主要方法:
- 利用最大的T-ALL瘤银行与79个新样本和54个公共样本的转录基因数据.
- 进行了计算分析和功能测试,以将线粒体活动与耐药性联系起来.
主要成果:
- 线粒体活动的下调驱动ABCB1激活,这是一个多药耐药基因.
- 脂肪酸氧化受损导致脂质积累,激活肝脏X受体 (LXRs) 和ABCB1表达.
- 高ABCB1表达与线粒体活性降低,脂质积累,攻击性增加和T-ALL患者的生存时间缩短有关.
结论:
- 减少的线粒体活性通过脂质介导的ABCB1激活诱导T-ALL中的多药性耐药性.
- 研究结果提供了对攻击性T-ALL生物学和化疗耐药性机制的见解.
- 针对新的脂质生成和食脂肪可以克服低线粒体活性T-ALL的治疗抵抗.
相关概念视频
Treatment Resistant Cancers
3.2K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.2K
Electron Transport Chain: Complex I and II
9.6K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
9.6K
Combination Therapies and Personalized Medicine
4.8K
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...
4.8K
Targeted Cancer Therapies
7.4K
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...
7.4K


