Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare neoplasm currently included among acute myeloid leukemias in the WHO classification. BPDCN is an orphan tumor characterized by an unknown biology with clinical aggressive course and dismal prognosis.

Only few studies explored its genetics, documenting a complex karyotype and sporadic genetic alterations. Unfortunately, data were based on a limited number of patients and lacked functional elucidation. Conversely, studies on the transcriptome only compared BPDCN with other leukemias, failing to identify pathogenetic events.

In this study we aimed to assess whether miRNA deregulation contribute to BPDCN pathogenesis and clinical behaviour.


We studied by miRNA profiling (NanoString Technologies) 30 BPDCN samples, 9 normal plasmacytoid dendritic cell (pDCs) samples and the CAL-1 tumor cell line. In addition, 25 independent BPDCN cases were studied by qRT-PCR and IHC as validation. To investigate the functional consequences of miRNA deregulation, we also performed a global gene expression profile (GEP) analysis on the same cases by using the Illumina Whole Genome DASL Assay. We applied ANOVA and Student t-test to find genes and miRNAs differentially expressed between BPDCNs and normal pDCs. The selected miRNAs were further filtered based on their predicted impact on the GEP using Linear Discriminant Analysis, Spearman correlation and Gene Set Enrichment Analysis. Finally, the functional effects of selected miRNAs were assessed ex vivo on CAL-1 cell line.


We found that, according to the unsupervised analysis of miRNAs, BPDCN patients have a molecular signature well distinct from their normal counterpart.

The following supervised analysis identified a set of 114 miRNAs significantly deregulated whose aberrant expression might have a relevant impact on cancer-related cellular pathways.

Therefore, after validating their expression in an independent set of cases, we integrated the miRNA and mRNA expression profiles on the same patients, in order to assess the functional impact of deregulated miRNAs on gene expression profile.

Pathway analysis of the predicted miRNA target genes, revealed that most of them were involved in the same gene ontology category: miRNAs synergic action appeared to strongly affect the biological process of programmed cell death.

We thus focused on miRNA-mRNA anti-correlations affecting the apoptotic pathway: we transfected specific mimics and inhibitors into CAL-1 cell line; we evaluated their functional impact by gene expression profile and, finally, we confirmed their relation with specific targets by Luciferase assay.

In conclusion, for the first time we investigated the miRNA profile of BPDCN, defining previously uncovered molecular mechanisms underlying the pathogenesis of the disease. Specifically, we found a subset of miRNAs significantly deregulated and highly affecting the apoptotic pathway.

Citation Format: Maria Rosaria Sapienza, Fabio Fuligni, Maria Antonella Laginestra, Maura Rossi, Luciano Cascione, Alessandro Laganà, Claudio Agostinelli, Maryam Etebari, Anna Gazzola, Claudia Mannu, Elena Sabattini, Francesco Bacci, Carlo Maria Croce, Stefano Aldo Pileri, Pier Paolo Piccaluga. miRNA expression profile of Blastic plasmacytoid dendritic cell neoplasm. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1951. doi:10.1158/1538-7445.AM2013-1951