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

IF 6 2区 医学 Q1 ONCOLOGY
Ruijuan Li, Wenyong Kuang, Haixia Yang, Benshan Zhang, Kexin Zhao, Weiyi Fang, Zhao Cheng, Xianming Fu, Hongling Peng
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引用次数: 0

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.

单细胞测序破译具有新型MYB-ZFAT融合基因的胚浆细胞样树突状细胞肿瘤的异质性景观。
背景:母浆细胞样树突状细胞肿瘤(BPDCN)是一种由浆细胞样树突状细胞前体引起的罕见的侵袭性血癌。它以CD4, CD56, CD123和CD303/CD304的表达为标志,涉及染色质缺失,突变和染色体易位等分子破坏。方法:本研究采用临床标本、组织学、FACS免疫分型、核型分析、转录组和蛋白结构分析、单细胞测序等综合方法,探讨BPDCN的分子基础。结果:该研究在BPDCN患者中发现了新的MYB-ZFAT基因融合,并显示出多样化的细胞群,与单一细胞类型理论相矛盾。它发现了四个主要的集群(集群1、2、3、8)和一个集群(集群12)具有独特的特征和在疾病进展中的作用。研究指出,T细胞受体信号转导、NK细胞细胞毒性和造血等关键通路参与了其发病机制。该研究强调了MYB激活在BPDCN细胞聚集和识别中的作用。结论:BPDCN具有不同细胞来源的复杂性,MYB活化在其发育过程中起重要作用。本研究加深了我们对BPDCN发病机制和细胞群的理解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
10.90
自引率
1.70%
发文量
360
审稿时长
1 months
期刊介绍: Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.
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