多组学单细胞测序确定混合表型急性白血病的干细胞性质

IF 14.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Cheryl A. C. Peretz, Vanessa E. Kennedy, Anushka Walia, Cyrille L. Delley, Andrew Koh, Elaine Tran, Iain C. Clark, Corey E. Hayford, Chris D’Amato, Yi Xue, Kristina M. Fontanez, Aaron A. May-Zhang, Trinity Smithers, Yigal Agam, Qian Wang, Hai-ping Dai, Ritu Roy, Aaron C. Logan, Alexander E. Perl, Adam Abate, Adam Olshen, Catherine C. Smith
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引用次数: 0

摘要

尽管最近有研究发现混合表型急性白血病(MPAL)与某些基因病变有关,但很大一部分患者的特定驱动基因突变仍未确定,而且没有任何基因亚型可预测临床结果。此外,MPAL 的治疗策略仍不明确,总体预后较差。我们对 14 名新确诊的成人 MPAL 患者进行了多组学单细胞图谱分析,以描述 MPAL 的瘤间和瘤内转录、免疫表型和遗传图谱。我们发现,基因图谱和转录组与特定的 MPAL 免疫表型都没有可靠的相关性。尽管如此,我们发现MPAL囊泡表达了一种类似干细胞的共同转录谱,表明其具有高分化潜能。在我们的数据集中,具有最高分化潜能的患者生存率较低。从干细胞样MPAL细胞中高度富集的基因中得出的基因组评分MPAL95适用于大容量RNA测序数据,并可预测独立患者队列的生存率,这为临床风险分层提供了一种潜在策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Multiomic single cell sequencing identifies stemlike nature of mixed phenotype acute leukemia

Multiomic single cell sequencing identifies stemlike nature of mixed phenotype acute leukemia

Despite recent work linking mixed phenotype acute leukemia (MPAL) to certain genetic lesions, specific driver mutations remain undefined for a significant proportion of patients and no genetic subtype is predictive of clinical outcomes. Moreover, therapeutic strategy for MPAL remains unclear, and prognosis is overall poor. We performed multiomic single cell profiling of 14 newly diagnosed adult MPAL patients to characterize the inter- and intra-tumoral transcriptional, immunophenotypic, and genetic landscapes of MPAL. We show that neither genetic profile nor transcriptome reliably correlate with specific MPAL immunophenotypes. Despite this, we find that MPAL blasts express a shared stem cell-like transcriptional profile indicative of high differentiation potential. Patients with the highest differentiation potential demonstrate inferior survival in our dataset. A gene set score, MPAL95, derived from genes highly enriched in the most stem-like MPAL cells, is applicable to bulk RNA sequencing data and is predictive of survival in an independent patient cohort, suggesting a potential strategy for clinical risk stratification.

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来源期刊
Nature Communications
Nature Communications Biological Science Disciplines-
CiteScore
24.90
自引率
2.40%
发文量
6928
审稿时长
3.7 months
期刊介绍: Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.
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