Abstract
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with poorly characterized molecular features. To identify disease-specific mutational profiles, we performed targeted next-generation sequencing (NGS) on a cohort of 21 BPDCN patients. Our study revealed that TET2 (57%) and ASXL1 (33%) were the most frequently mutated genes, followed by NRAS (29%), SRSF2 (14%), ZRSR2 (14%), and KMT2D (14%). Further analysis demonstrated that poor prognosis was associated with older age (≥65 years), the presence of three or more mutations, TET2 mutations, TET2 truncating mutations, and mutations involving DNA methylation pathways. In contrast, patients who underwent hematopoietic stem cell transplantation (HSCT) exhibited more favorable clinical outcomes. Moreover, our study indicated that CCDC50 expression was significantly elevated in BPDCN cases compared to those with acute myeloid leukemia (AML) or chronic monomyelocytic leukemia (CMML), suggesting that CCDC50 may serve as a reliable diagnostic marker for distinguishing BPDCN from AML, as well as a potential biomarker for disease monitoring. Finally, our investigation of mutational profiles in sequentially paired specimens revealed a high prevalence of bone marrow clonal hematopoiesis in patients with BPDCN. In conclusion, the genetic landscape of BPDCN identified in this study provides valuable insights that may improve diagnostic accuracy and guide prognostic evaluation and therapeutic strategies. However, validation in larger, independent cohorts are warranted.