急性髓性白血病的单细胞染色质可访问性概况显示,在治疗耐药性方面,异构的血统组成
Huihui Fan1,2, Feng Wang3, Andy Zeng4,5
1Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Communications biology
|July 21, 2023
概括
耐治疗的急性髓性白血病 (AML) 细胞表现出多种谱系组成,包括干细胞,原始细胞和分化状态. 这种异质性涉及髓状,红状和淋巴状血统,有助于治疗耐药性并影响预后.
科学领域:
- 血液学 血液学 血液学
- 癌症生物学 癌症生物学
- 基因组学就是基因组学.
背景情况:
- 急性髓性白血病 (AML) 是一种复杂的血液癌症,以高治疗耐药率而闻名.
- 了解AML的细胞起源和血统可塑性对于改善治疗结果至关重要.
研究的目的:
- 为了研究治疗耐药AML细胞的血统景观.
- 在治疗耐药性期间,在单细胞水平上描述AML细胞的异质性.
主要方法:
- 单细胞染色体可访问性分析 (scATAC-seq) 对来自AML患者的骨髓吸收剂进行.
- 分析包括治疗耐药性的时间和随后治疗后的样本.
- 伪素体分析被用来评估染色质可访问性和谱系轨迹的动态变化.
主要成果:
- 耐治疗的AML细胞表现出复杂的谱系架构,为干细胞和原始细胞状态 (静止,激活,晚期) 做准备.
- 值得注意的是,耐药AML细胞也表现出对分化髓状,红状腺和淋巴状细胞系的原始化.
- 这种血统异质性在治疗后仍然存在,并且与不良预后有关,如癌症基因组图谱 (TCGA) AML队列中所见.
结论:
- 耐治疗AML的特点是细胞系的连续性,而不仅仅是干细胞/祖细胞状态.
- 观察到的血统异质性可能会通过呈现各种血统特定的脆弱性来驱动治疗耐药性.
- 准这种细胞可塑性可能为AML提供新的治疗策略.
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