New perspectives in genetics and targeted therapy for blastic plasmacytoid dendritic cell neoplasm.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is one rare but clinically aggressive hematological malignancy, and it is typically characterized by skin lesion and bone marrow involvement. Diagnosis of BPDCN relies on the immunophenotype positive for four of CD4, CD56, CD123, TCL1 and BDCA-2, and commonly without the expression of MPO, cytoplasmic CD3, CD13, CD64, cytoplasmic CD79a, CD19 and CD20. Commonly, BPDCN is characterized by high CD123 expression, aberrant NF-κB activation, dependence on TCF4-/BRD4-network, and deregulated cholesterol metabolism. Under conventional therapy, the survival duration is only improved in a small number of BPDCN patients. Therefore, targeted therapy should be developed. Up to now, tagraxofusp is the leading edge and has been approved for BPDCN treatment. However, most of other targeted therapy agents were still not pushed to clinical trials for BPDCN. In this review, we emphatically discuss recent perspectives on BPDCN genetic features and developments of its targeted therapy.