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

Abstract 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...

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Main Authors: Ruijuan Li, Wenyong Kuang, Haixia Yang, Benshan Zhang, Kexin Zhao, Weiyi Fang, Zhao Cheng, Xianming Fu, Hongling Peng
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Cancer Cell International
Online Access:https://doi.org/10.1186/s12935-025-03899-4
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author Ruijuan Li
Wenyong Kuang
Haixia Yang
Benshan Zhang
Kexin Zhao
Weiyi Fang
Zhao Cheng
Xianming Fu
Hongling Peng
author_facet Ruijuan Li
Wenyong Kuang
Haixia Yang
Benshan Zhang
Kexin Zhao
Weiyi Fang
Zhao Cheng
Xianming Fu
Hongling Peng
author_sort Ruijuan Li
collection DOAJ
description Abstract 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.
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institution Kabale University
issn 1475-2867
language English
publishDate 2025-07-01
publisher BMC
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series Cancer Cell International
spelling doaj-art-6fa775f7e1474bc19361fabefbe55b722025-08-20T03:46:16ZengBMCCancer Cell International1475-28672025-07-0125112310.1186/s12935-025-03899-4Single cell sequencing deciphering the heterogeneous landscape of blastic plasmacytoid dendritic cell neoplasm with novel MYB-ZFAT fusion geneRuijuan Li0Wenyong Kuang1Haixia Yang2Benshan Zhang3Kexin Zhao4Weiyi Fang5Zhao Cheng6Xianming Fu7Hongling Peng8Department of Hematology, The Second Xiangya Hospital, Central South UniversityDepartment of Hematology, The Affiliated Children’s Hospital Of Xiangya School of Medicine, Central South UniversityDepartment of Hematology, The Affiliated Children’s Hospital Of Xiangya School of Medicine, Central South UniversityDepartment of Hematology, The Affiliated Children’s Hospital Of Xiangya School of Medicine, Central South UniversityDepartment of Hematology, The Second Xiangya Hospital, Central South UniversityDepartment of Hematology, The Second Xiangya Hospital, Central South UniversityDepartment of Hematology, The Second Xiangya Hospital, Central South UniversityDepartment of Cardiovascular Surgery, The Second Xiangya Hospital, Central South UniversityDepartment of Hematology, The Second Xiangya Hospital, Central South UniversityAbstract 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.https://doi.org/10.1186/s12935-025-03899-4
spellingShingle Ruijuan Li
Wenyong Kuang
Haixia Yang
Benshan Zhang
Kexin Zhao
Weiyi Fang
Zhao Cheng
Xianming Fu
Hongling Peng
Single cell sequencing deciphering the heterogeneous landscape of blastic plasmacytoid dendritic cell neoplasm with novel MYB-ZFAT fusion gene
Cancer Cell International
title Single cell sequencing deciphering the heterogeneous landscape of blastic plasmacytoid dendritic cell neoplasm with novel MYB-ZFAT fusion gene
title_full Single cell sequencing deciphering the heterogeneous landscape of blastic plasmacytoid dendritic cell neoplasm with novel MYB-ZFAT fusion gene
title_fullStr Single cell sequencing deciphering the heterogeneous landscape of blastic plasmacytoid dendritic cell neoplasm with novel MYB-ZFAT fusion gene
title_full_unstemmed Single cell sequencing deciphering the heterogeneous landscape of blastic plasmacytoid dendritic cell neoplasm with novel MYB-ZFAT fusion gene
title_short Single cell sequencing deciphering the heterogeneous landscape of blastic plasmacytoid dendritic cell neoplasm with novel MYB-ZFAT fusion gene
title_sort single cell sequencing deciphering the heterogeneous landscape of blastic plasmacytoid dendritic cell neoplasm with novel myb zfat fusion gene
url https://doi.org/10.1186/s12935-025-03899-4
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