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重塑B细胞前体急性淋巴细胞白血病细胞的糖体,这些细胞在发展药物耐受性时会发生重塑
bioRxiv : the preprint server for biology
|September 4, 2024
概括
药物耐受性前体B型急性淋巴细胞白血病细胞表现出改变的细胞表面甘氨酸,包括O-甘氨酸和N-甘氨酸的变化,可能导致化疗耐药性.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 在瘤学瘤学.
背景情况:
- 在前体B型急性淋巴细胞白血病 (BCP-ALL) 中,最小的残留疾病表明化疗反应减少.
- 骨髓的微环境支持白血病细胞的生存和耐药性.
- 糖化,一个关键的细胞表面修饰,在耐药白血病细胞中基本上没有特征.
研究的目的:
- 为了研究BCP-ALL细胞对温克里斯化学疗法的耐受性.
- 为了确定与药物耐受性和存活相关的特定糖化变化.
主要方法:
- 对与骨髓 stromal 细胞共培养的 BCP-ALL 细胞进行的 omics 分析 (proteomics, glycomics, glycoproteomics).
- 用温克里斯化学疗法治疗细胞30天.
- 对糖化酶的mRNA表达的分析.
主要成果:
- 蛋白质组学揭示了代谢酶水平的降低.
- 糖核的改变包括从Core-2转向Core-1 O-glycans,并减少了化.
- 增加的两截复合N-甘氨酸与增加的MGAT3mRNA表达相关.
- 糖蛋白组学确定了HLA-DRA,CD38,LAMP1和PPT1.1等蛋白质的特定位点的糖化变化.
结论:
- 耐药性持久性BCP-ALL细胞在化疗压力下表现出明显的葡萄糖特征.
- 这些甘氨酸变化可能有助于白血病细胞存活率和耐药性.
- 具有特征的甘氨酸变化可以作为潜在的新抗原来向耐药白血病.
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