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

作者：Ruijuan Li, Wenyong Kuang, Haixia Yang, Benshan Zhang, Kexin Zhao, Weiyi Fang, Zhao Cheng, Xianming Fu, Hongling Peng · 发表于：Cancer Cell International · 年份：2025 · DOI：10.1186/s12935-025-03899-4 · 被引用次数：1 · 研究领域：Cutaneous lymphoproliferative disorders research、Histiocytic Disorders and Treatments、Immunotherapy and Immune Responses

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.