Multiomic Single Cell Sequencing Identifies Stemlike Nature of Mixed Phenotype Acute Leukemia and Provides Novel Risk Stratification.
Multiomic Single Cell Sequencing Identifies Stemlike Nature of Mixed Phenotype Acute Leukemia and Provides Novel Risk Stratification.
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多组学单细胞测序鉴定了混合表型急性白血病的干细胞性质，并提供了新的风险分层。
DOI：
10.1101/2023.05.15.540305
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发表时间：
2023
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作者：
Peretz,CherylAC;Kennedy,VanessaE;Walia,Anushka;Delley,CyrilleL;Koh,Andrew;Tran,Elaine;Clark,IainC;Hayford,CoreyE;D'Amato,Chris;Xue,Yi;Fontanez,KristinaM;Roy,Ritu;Logan,AaronC;Perl,AlexanderE;Abate,Adam;Olshen,Adam;
混合表型急性白血病（MPAL）是一种生物学驱动机制尚不清楚、治疗策略尚不明确、预后较差的白血病。我们对14名新诊断的成年MPAL患者进行了多组单细胞（SC）分析，以表征MPAL的免疫表型、遗传和转录特征。我们表明，无论是遗传谱还是转录组都不能可靠地与特定的MPAL免疫表型相关。然而，突变的渐进获得与不成熟的免疫表型标记物的表达增加有关。通过SC转录谱分析，我们发现MPAL细胞表达了与其他急性白血病不同的干细胞样转录谱，表明其具有高分化潜力。此外，分化潜力最高的患者在我们的数据集中表现出较低的生存率。MPAL95基因集评分来源于该队列中高度富集的基因，适用于大量RNA测序数据，并可预测独立患者队列的生存，提示临床风险分层的实用性。
Mixed phenotype acute leukemia (MPAL) is a leukemia whose biologic drivers are poorly understood, therapeutic strategy remains unclear, and prognosis is poor. We performed multiomic single cell (SC) profiling of 14 newly diagnosed adult MPAL patients to characterize the immunophenotypic, genetic, and transcriptional landscapes of MPAL. We show that neither genetic profile nor transcriptome reliably correlate with specific MPAL immunophenotypes. However, progressive acquisition of mutations is associated with increased expression of immunophenotypic markers of immaturity. Using SC transcriptional profiling, we find that MPAL blasts express a stem cell-like transcriptional profile distinct from other acute leukemias and indicative of high differentiation potential. Further, patients with the highest differentiation potential demonstrated inferior survival in our dataset. A gene set score, MPAL95, derived from genes highly enriched in this cohort, is applicable to bulk RNA sequencing data and was predictive of survival in an independent patient cohort, suggesting utility for clinical risk stratification.