Multiomic Single Cell Sequencing Identifies Stemlike Nature of Mixed Phenotype Acute Leukemia and Provides Novel Risk Stratification [PIP-seq]

Mixed phenotype acute leukemia (MPAL) also known as acute leukemia of ambiguous lineage (ALAL), is characterized by leukemic blasts with both lymphoid and myeloid cell surface markers. Here, we use SC multiomic profiling on newly diagnosed MPAL samples to characterize the immunophenotypic, genetic, and transcriptional landscapes of MPAL. This profiling allows us to definitively contradict the paradigm of MPAL as a disease on a continuum with myeloid and lymphoid lineage acute leukemias, and instead identifies MPAL as a distinct, stem-like disease that, unlike other leukemias, cannot be defined by genetics alone. We further describe a stem cell gene expression signature for MPAL that can predict patient survival. These results broaden our understanding of MPAL biology and suggest a path toward novel risk stratification for MPAL. Importantly, these findings have potential to direct treatment and, hopefully, ultimately improve the prognosis of this disease. Samples from 14 adult patients with de novo MPAL were analyzed for single cell DNA, RNA, protein.

混合表型急性白血病（Mixed phenotype acute leukemia，MPAL），亦称不明系别急性白血病（acute leukemia of ambiguous lineage，ALAL），以同时表达淋巴系与髓系细胞表面标志物的白血病原始细胞为核心特征。本研究对新确诊的MPAL样本开展单细胞多组学分析，以此刻画MPAL的免疫表型、遗传特征与转录组全景。该分析使我们能够明确驳斥「MPAL是介于髓系与淋巴系急性白血病之间的连续疾病谱系」这一主流认知范式，转而证实MPAL是一种独特的干细胞样疾病——与其他白血病不同，MPAL无法仅通过遗传学特征完成定义。本研究进一步揭示了可预测患者生存预后的MPAL干细胞基因表达特征。上述研究结果拓展了我们对MPAL生物学特性的认知，并为MPAL的新型风险分层策略指明了方向。尤为重要的是，这些发现有望指导临床治疗，并最终改善该疾病的预后。本研究对14例新发（de novo）MPAL成人患者的样本进行了单细胞DNA、RNA与蛋白质层面的分析。