单细胞测序揭示具有新型MYB-ZFAT融合基因的母细胞样浆细胞样树突状细胞瘤的异质性景观。

Single cell sequencing deciphering the heterogeneous landscape of blastic plasmacytoid dendritic cell neoplasm with novel MYB-ZFAT fusion gene.

作者信息

Li Ruijuan, Kuang Wenyong, Yang Haixia, Zhang Benshan, Zhao Kexin, Fang Weiyi, Cheng Zhao, Fu Xianming, Peng Hongling

机构信息

Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Department of Hematology, The Affiliated Children's Hospital Of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.

出版信息

Cancer Cell Int. 2025 Jul 21;25(1):274. doi: 10.1186/s12935-025-03899-4.

BACKGROUND

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive blood cancer from plasmacytoid dendritic cell precursors. It's marked by CD4, CD56, CD123, and CD303/CD304 expression and involves molecular disruptions like chromatin deletions, mutations, and chromosomal translocations.

METHODS

The current study employed a comprehensive method with clinical samples, histology, FACS immunophenotyping, karyotype analysis, transcriptome and protein structure analysis, and single-cell sequencing to explore BPDCN's molecular basis.

RESULTS

The study discovered a new MYB-ZFAT gene fusion in a BPDCN patient and showed a diverse cell population, contradicting a single cell type theory. It found four major clusters (Cluster 1,2,3,8 ) and one cluster (clulster 12) with unique profiles and roles in disease progression. The research noted Key pathways include T cell receptor signaling, NK cell cytotoxicity, and hematopoiesis are involved in pathogenesis. The study emphasized MYB activation's role in BPDCN's cellular clustering and identity.

CONCLUSION

The study indicates BPDCN's complexity with varied cellular origins and a significant role for MYB activation in its development. This research deepens our comprehension of BPDCN's pathogenesis and cell populations.

背景

母细胞样浆细胞样树突状细胞瘤（BPDCN）是一种罕见的侵袭性血癌，起源于浆细胞样树突状细胞前体。它以CD4、CD56、CD123和CD303/CD304表达为特征，涉及染色质缺失、突变和染色体易位等分子破坏。

方法

本研究采用综合方法，结合临床样本、组织学、流式细胞术免疫表型分析、核型分析、转录组和蛋白质结构分析以及单细胞测序，以探索BPDCN的分子基础。

结果

该研究在一名BPDCN患者中发现了一种新的MYB-ZFAT基因融合，并显示出多样化的细胞群体，这与单一细胞类型理论相矛盾。它发现了四个主要簇（簇1、2、3、8）和一个具有独特特征且在疾病进展中起作用的簇（簇12）。研究指出关键途径包括T细胞受体信号传导、NK细胞细胞毒性和造血作用均参与发病机制。该研究强调了MYB激活在BPDCN细胞聚集和特征形成中的作用。