相关实验视频

Updated: Jul 20, 2025

Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype

Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype

Published on: June 17, 2022

在NUP98重新排列的AML中,MLL-Menin相互作用是一种治疗脆弱性

Milad Rasouli^1,2, Helen Blair³, Selina Troester⁴

¹Princess Maxima Center for pediatric Oncology, Utrecht, The Netherlands.

|July 31, 2023

概括

针对Menin-MLL与revumenib的相互作用抑制了NUP98融合的儿科急性髓性白血病 (AML). 这种Menin抑制剂疗法减少了白血病细胞的生长,并改善了临床前模型的结果.

科学领域:

血液学血液学血液学
在瘤学瘤学.
分子生物学分子生物学

背景情况:

涉及NUP98位点的染色体转位在儿科急性髓性白血病 (AML) 中很常见.
NUP98的融合导致高的HOXA和MEIS1基因表达,与预后不佳相关.
NUP98融合蛋白依赖于Menin-MLL相互作用来招募目标基因.

研究的目的:

调查针对NUP98重组的AML中的Menin-MLL相互作用的有效性.
在临床前AML模型中评估Menin抑制剂revumenib (SNDX-5613) 的治疗潜力.

主要方法:

使用revumenib对初级AML细胞进行体外治疗.
在体内研究中,使用与患者衍生的AML细胞移植的小鼠模型.
对基因表达变化和与FLT3抑制剂的药物协同作用的分析.

主要成果:

雷文尼布损害了NUP98重新排列的AML细胞的扩散和克隆原性.
治疗下调了关键的NUP98融合基因,包括MEIS1和CDK6.
单独或与FLT3抑制剂一起使用的revumenib抑制了白血病的生长,并改善了体内生存率.

结论:

NUP98重组的AML对Menin-MLL相互作用的抑制敏感.
雷文尼布证明了NUP98重新安排的AML的治疗潜力.
梅因抑制剂需要对NUP98融合的AML患者进行临床评估.

更多相关视频

Rapid Analysis of Chromosome Aberrations in Mouse B Lymphocytes by PNA-FISH

Rapid Analysis of Chromosome Aberrations in Mouse B Lymphocytes by PNA-FISH

Published on: August 19, 2014

Investigation of Genetic Dependencies Using CRISPR-Cas9-based Competition Assays

Investigation of Genetic Dependencies Using CRISPR-Cas9-based Competition Assays

Published on: January 7, 2019

相关概念视频

Mismatch Repair

Mismatch Repair

Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...

Abnormal Proliferation

Abnormal Proliferation

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...