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B细胞急性淋巴细胞白血病中的多系分化潜能与不同细胞起源及临床特征相关

Multipotent lineage potential in B cell acute lymphoblastic leukemia is associated with distinct cellular origins and clinical features

原文发布日期：2025-06-27

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B细胞急性淋巴细胞白血病中的多系分化潜能与不同细胞起源及临床特征相关

Multipotent lineage potential in B cell acute lymphoblastic leukemia is associated with distinct cellular origins and clinical features

原文发布日期：2025-06-27

英文摘要：

Developmental origins and their associations with lineage plasticity and treatment response in B-cell progenitor acute lymphoblastic leukemia (B-ALL) are mostly unexplored. Here, we integrated single-cell transcriptome sequencing (scRNA-seq) of 89 B-ALL samples with a single-cell atlas of normal human B cell development incorporating functional and molecular assays. We observed subtype- and sample-dependent correlation with normal developmental stage, with intra-subtype and intra-patient heterogeneity. We show that subtypes prone to shift from the B-lineage (for example BCR::ABL1, KMT2A-R and DUX4-R B-ALL) are enriched for multipotent progenitors and show this developmental stage exhibits CEBPA activation and retains myeloid potential, providing a mechanistic explanation for this clinical observation. We developed a ‘multipotency score’ most enriched in subtypes exhibiting lineage plasticity that was independently associated with inferior survival. Thus, multipotent B-ALL states reflect the early progenitor origins of a subset of patients with B-ALL and may be relevant for understanding lineage shifting following conventional chemotherapy or immunotherapies.

摘要翻译：

B细胞前体急性淋巴细胞白血病（B-ALL）的发育起源及其与谱系可塑性、治疗反应的关联目前尚不明确。本研究整合了89例B-ALL样本的单细胞转录组测序（scRNA-seq）数据与正常人B细胞发育的单细胞图谱，并结合功能及分子实验分析。我们发现：不同亚型及样本与正常发育阶段存在相关性，且具有亚型内和患者内的异质性；易发生B系转换的亚型（如BCR::ABL1、KMT2A-R和DUX4-R B-ALL）富含多能祖细胞，该发育阶段呈现CEBPA激活并保留髓系分化潜能，为此临床现象提供了机制解释。我们开发的"多能性评分"在表现谱系可塑性的亚型中富集程度最高，且与不良预后独立相关。因此，B-ALL的多能性状态反映了一部分患者的早期祖细胞起源特征，这对理解传统化疗或免疫治疗后出现的谱系转换现象具有重要意义。