Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy originating from precursors of plasmacytoid dendritic cells. This study aimed to understand the relationship between malignant clones in different tissues and determine new biomarkers to improve the management of BPDCN.
Methods: We conducted a comprehensive analysis by integrating single-cell transcriptomic data from bone marrow (BM)-derived cells, peripheral blood mononuclear cells (PBMCs), and skin-derived cells from one BPDCN patient and matched healthy controls (HCs). Validation was performed in two independent cohorts consisting of 12 BPDCN patients and control groups, including common skin tumors, cutaneous lymphomas, inflammatory skin diseases and HCs.
Results: Our study revealed that malignant cells in the skin exhibited greater maturity and differentiation compared with those from BMs, suggesting that the BM is a more likely origin for BPDCN. Additionally, malignant cells across different tissues in the BPDCN patient displayed significant transcriptional heterogeneity. The multiplex immunohistochemistry (mIHC) analysis revealed that the expression of PLD4 was significantly elevated in the dermis of BPDCN patients compared with the control groups. Furthermore, most PLD4-positive cells were found to co-localize with CD123 in BPDCN skin lesions.
Conclusions: This study suggested a potential clonal origin of tumor cells, and revealed the transcriptional heterogeneity among malignant cells across different tissues in BPDCN. PLD4 was identified as a specific marker of malignant cells, aiding in the diagnosis of BPDCN and showing potential as a therapeutic target.
Keywords: Blastic plasmacytoid dendritic cell neoplasm (BPDCN); PLD4; Single-cell analyses.
© 2025. The Author(s).