混合表型急性白血病的遗传基础和细胞来源
Thomas B Alexander1,2, Zhaohui Gu3, Ilaria Iacobucci3
1Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Nature
|September 14, 2018
概括
混合表型急性白血病 (MPAL) 亚型在遗传上是不同的,T/骨髓和B/骨髓MPAL的特异性变化. 这些发现揭示了源细胞和创始病变驱动MPAL,为未来的临床试验提供了信息.
科学领域:
- 血液学
- 癌症学
- 遗传学
背景情况:
- 混合表型急性白血病 (MPAL) 是一种具有髓状和淋巴状特征的高风险白血病.
- 由于有限的遗传特征和治疗共识,MPAL存在挑战.
研究的目的:
- 在基因上描述MPAL的两个主要亚型:T/myeloid (T/M) 和B/myeloid (B/M).
- 调查MPAL免疫类型异质性的起源及其与遗传变化的关系.
主要方法:
- 对T/M和B/MMPAL亚型进行基因组比较分析.
- 研究体质遗传变异及其对免疫类型异质性的影响.
- 在MPAL发育中分析创始病变和起源细胞.
主要成果:
- T/M MPAL和B/M MPAL是基因上不同的亚型.
- 在B/MMPAL中,ZNF384的重组是常见的;在T/MMPAL中,双基WT1的改变是普遍的.
- 免疫类型异质性是独立于体质遗传学,原始祖先的创始病变.
结论:
- MPAL的血统变异是由起源细胞和创始病变驱动的,而不是仅仅是累积的基因组变化.
- MPAL属于未成熟白血病的范围.
- 这些发现为MPAL治疗策略和临床试验提供了基因框架.
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