微环境中的素可以在急性淋巴细胞白血病中激活氨酸耐药性
Xiaohong Wang1,2, Jason Ostergaard1,2, Jongseok Kang1,2
1Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of Minnesota, Minneapolis, MN, United States.
Frontiers in oncology
|August 5, 2024
概括
瘤微环境中的低素降低了急性淋巴细胞白血病 (ALL) 类型的提奥普林化疗的有效性. 这一发现在一个更现实的ex vivo模型中突出了小儿白血病中药物耐药性的机制.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 癌症生物学 癌症生物学
背景情况:
- 急性淋巴细胞白血病 (ALL) 是最常见的儿童癌症.
- 由于化疗耐药性的复发仍然是治疗儿科ALL的一个重大挑战.
- 瘤微环境在药物耐药性中的作用尚未完全理解.
研究的目的:
- 研究瘤微环境对白血病细胞药物反应的影响.
- 确定儿科ALL中化疗耐药性的机制.
- 评估人类等离子体类介质 (HPLM) 对研究药物耐药性的实体效用.
主要方法:
- 利用类似于人体血的介质 (HPLM) 来模仿生理条件ex vivo.
- 评估了各种化疗药物对HPLM和标准介质中的B型和T型白血病细胞的疗效.
- 研究了素在赋予对氨酸 (6-氨酸和6-氨酸) 耐药性的作用.
主要成果:
- 与标准介质相比,蒂奥普林 (6-默卡普托普林和6-蒂奥瓜宁) 在HPLM中显著降低了功效和疗效.
- 鉴定出海普丁是导致提奥普林耐药性的代谢物.
- 耐药性所需的低素度在生理上与体内条件相关.
结论:
- 人体等离子体介质 (HPLM) 是发现微环境介导的耐药性机制的宝贵工具.
- 低素在儿科白血病细胞中赋予了对 thiopurines 的耐药性.
- 了解这些相互作用可以指导克服药物耐药性的策略,并改善儿科ALL的结果.
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