相关实验视频

Updated: Jul 23, 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

流体诱导的上皮质-介质细胞转换诱导了急性淋巴细胞白血病的可向药物耐药性

Chun Shik Park¹, Hiroki Yoshihara¹, Qingsong Gao¹

¹Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

|July 15, 2023

概括

急性淋巴细胞白血病 (ALL) 的耐药性是由与骨髓中介细胞干细胞 (MSC) 的相互作用驱动的. 针对WNT/β-catenin通路可以克服这种阻力.

科学领域:

血液学血液学血液学
癌症生物学癌症生物学
细胞生物学细胞生物学

背景情况:

骨髓微环境 (BME) 对急性淋巴细胞白血病 (ALL) 的进展和药物耐药性至关重要.
骨髓赋予ALL中药物耐药性的机制尚未完全理解.

研究的目的:

阐明由骨髓介质干细胞 (MSCs) 介导的ALL中药物耐药性背后的机制.
确定潜在的治疗点,以克服ALL中药物耐药性.

主要方法:

与MSCs共同培养的ALL细胞.
单细胞RNA测序 (scRNA-seq) 的分析.
在体外和体外药物耐药性测试.
针对WNT/β-catenin通路相互作用的向.

主要成果:

通过整体蛋白β1的ALL和MSC之间的相互作用会在ALL细胞中诱导类似于上皮质-介质细胞过渡 (EMT) 的程序,增强存活率和耐药性.
scRNA-seq发现了一种由WNT/β-catenin介导的EMT类程序驱动的混合ALL-MSC细胞群.
阻断β-catenin和CREB结合蛋白相互作用减少了ALL细胞存活率和药物耐药性在体外,并在体内减少了白血病负担.

结论:

在MSC附着ALL细胞中的WNT/β-catenin介导的EMT类程序是获得药物耐药性的关键机制.
准这种途径是一个有希望的治疗策略,以克服ALL的耐药性.

关键词:

所有的,所有的,所有的.CP: 癌症癌症癌症在WNT中使用WNT.急性淋巴细胞白血病急性淋巴细胞白血病骨髓微环境骨髓微环境细胞粘附细胞粘附细胞与细胞的相互作用.化学电阻是一种化学电阻.药物耐药性耐药性药物耐药性表皮细胞-介质细胞过渡.中介细胞干细胞中介细胞干细胞.

更多相关视频

Modeling Chemotherapy Resistant Leukemia In Vitro

Modeling Chemotherapy Resistant Leukemia In Vitro

Published on: February 9, 2016

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells

Published on: April 7, 2017

相关概念视频

Treatment Resistant Cancers

Treatment Resistant Cancers

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...

Cancer Stem Cells and Tumor Maintenance

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...

Metastasis

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...