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Leukemia. 2014 Aug;28(8):1606-16. doi: 10.1038/leu.2014.64. Epub 2014 Feb 7.

Molecular profiling of blastic plasmacytoid dendritic cell neoplasm reveals a unique pattern and suggests selective sensitivity to NF-kB pathway inhibition.

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Department of Experimental, Diagnostic, and Specialty Medicine, Hematopathology & Hematology Sections, Molecular Pathology Laboratory, S. Orsola-Malpighi Hospital, Bologna University, Bologna, Italy.
Department of Health Science, Tumour Immunology Unit, Human Pathology Section University of Palermo School of Medicine, Palermo, Italy.
Department of Surgery and Translational Medicine - Division Dermatology, University of Florence, Florence, Italy.
Department of Hematology, Oncology and Laboratory Medicine, Transfusion Medicine Service, S. Orsola-Malpighi Hospital, Bologna, Italy.
Anatomic Pathology Section, University of Pavia Medical School, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Fondazione Policlinico, San Matteo, Pavia, Italy.
Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Department of Experimental, Diagnostic, and Specialty Medicine, Microbiology Section, S. Orsola-Malpighi Hospital, Bologna University, Bologna, Italy.
Institute of Hematology, Catholic University, Rome, Italy.
Department of Surgery and Translational Medicine, Pathologic Anatomy Division, University of Florence, Florence, Italy.
Department of Dermatology, Medical University of Graz, Graz, Austria.
Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Department of Molecular and Translational Medicine, Pathology Section, University of Brescia, Brescia, Italy.


Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare disease of controversial origin recently recognized as a neoplasm deriving from plasmacytoid dendritic cells (pDCs). Nevertheless, it remains an orphan tumor with obscure biology and dismal prognosis. To better understand the pathobiology of BPDCN and discover new targets for effective therapies, the gene expression profile (GEP) of 25 BPDCN samples was analyzed and compared with that of pDCs, their postulated normal counterpart. Validation was performed by immunohistochemistry (IHC), whereas functional experiments were carried out ex vivo. For the first time at the molecular level, we definitely recognized the cellular derivation of BPDCN that proved to originate from the myeloid lineage and in particular, from resting pDCs. Furthermore, thanks to an integrated bioinformatic approach we discovered aberrant activation of the NF-kB pathway and suggested it as a novel therapeutic target. We tested the efficacy of anti-NF-kB-treatment on the BPDCN cell line CAL-1, and successfully demonstrated by GEP and IHC the molecular shutoff of the NF-kB pathway. In conclusion, we identified a molecular signature representative of the transcriptional abnormalities of BPDCN and developed a cellular model proposing a novel therapeutic approach in the setting of this otherwise incurable disease.

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