Evidence map›Paper›PMID 24504027›Full record

ArticleLeukemia2014

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

M R Sapienza, F Fuligni, C Agostinelli, C Tripodo, S Righi, M A Laginestra, A Pileri, M Mancini, M Rossi, F Ricci and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Leukemia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.

0numbers the graph read from it
0cells of the map it votes in
96citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

96 citing papers in PubMed.

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36 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

27 authors.

M R SapienzaDepartment of Experimental, Diagnostic, and Specialty Medicine, Hematopathology & Hematology Sections, Molecular Pathology Laboratory, S. Orsola-Malpighi Hospital, Bologna University, Bologna, Italy.
F FuligniDepartment of Experimental, Diagnostic, and Specialty Medicine, Hematopathology & Hematology Sections, Molecular Pathology Laboratory, S. Orsola-Malpighi Hospital, Bologna University, Bologna, Italy.
C AgostinelliDepartment of Experimental, Diagnostic, and Specialty Medicine, Hematopathology & Hematology Sections, Molecular Pathology Laboratory, S. Orsola-Malpighi Hospital, Bologna University, Bologna, Italy.
C TripodoDepartment of Health Science, Tumour Immunology Unit, Human Pathology Section University of Palermo School of Medicine, Palermo, Italy.
S RighiDepartment of Experimental, Diagnostic, and Specialty Medicine, Hematopathology & Hematology Sections, Molecular Pathology Laboratory, S. Orsola-Malpighi Hospital, Bologna University, Bologna, Italy.
M A LaginestraDepartment of Experimental, Diagnostic, and Specialty Medicine, Hematopathology & Hematology Sections, Molecular Pathology Laboratory, S. Orsola-Malpighi Hospital, Bologna University, Bologna, Italy.
A PileriDepartment of Surgery and Translational Medicine - Division Dermatology, University of Florence, Florence, Italy.
M ManciniDepartment of Experimental, Diagnostic, and Specialty Medicine, Hematopathology & Hematology Sections, Molecular Pathology Laboratory, S. Orsola-Malpighi Hospital, Bologna University, Bologna, Italy.
M RossiDepartment of Experimental, Diagnostic, and Specialty Medicine, Hematopathology & Hematology Sections, Molecular Pathology Laboratory, S. Orsola-Malpighi Hospital, Bologna University, Bologna, Italy.
F RicciDepartment of Hematology, Oncology and Laboratory Medicine, Transfusion Medicine Service, S. Orsola-Malpighi Hospital, Bologna, Italy.
A GazzolaDepartment of Experimental, Diagnostic, and Specialty Medicine, Hematopathology & Hematology Sections, Molecular Pathology Laboratory, S. Orsola-Malpighi Hospital, Bologna University, Bologna, Italy.
F MelleDepartment of Experimental, Diagnostic, and Specialty Medicine, Hematopathology & Hematology Sections, Molecular Pathology Laboratory, S. Orsola-Malpighi Hospital, Bologna University, Bologna, Italy.
C MannuDepartment of Experimental, Diagnostic, and Specialty Medicine, Hematopathology & Hematology Sections, Molecular Pathology Laboratory, S. Orsola-Malpighi Hospital, Bologna University, Bologna, Italy.
F UlbarDepartment of Experimental, Diagnostic, and Specialty Medicine, Hematopathology & Hematology Sections, Molecular Pathology Laboratory, S. Orsola-Malpighi Hospital, Bologna University, Bologna, Italy.
M ArpinatiDepartment of Experimental, Diagnostic, and Specialty Medicine, Hematopathology & Hematology Sections, Molecular Pathology Laboratory, S. Orsola-Malpighi Hospital, Bologna University, Bologna, Italy.
M PaulliAnatomic Pathology Section, University of Pavia Medical School, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Fondazione Policlinico, San Matteo, Pavia, Italy.
T MaedaDepartment of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
D GibelliniDepartment of Experimental, Diagnostic, and Specialty Medicine, Microbiology Section, S. Orsola-Malpighi Hospital, Bologna University, Bologna, Italy.
L PaganoInstitute of Hematology, Catholic University, Rome, Italy.
N PimpinelliDepartment of Surgery and Translational Medicine - Division Dermatology, University of Florence, Florence, Italy.
M SantucciDepartment of Surgery and Translational Medicine, Pathologic Anatomy Division, University of Florence, Florence, Italy.
L CerroniDepartment of Dermatology, Medical University of Graz, Graz, Austria.
C M CroceDepartment of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
F FacchettiDepartment of Molecular and Translational Medicine, Pathology Section, University of Brescia, Brescia, Italy.
P P PiccalugaDepartment of Experimental, Diagnostic, and Specialty Medicine, Hematopathology & Hematology Sections, Molecular Pathology Laboratory, S. Orsola-Malpighi Hospital, Bologna University, Bologna, Italy.ORCID 0000000294320595
S A PileriDepartment of Experimental, Diagnostic, and Specialty Medicine, Hematopathology & Hematology Sections, Molecular Pathology Laboratory, S. Orsola-Malpighi Hospital, Bologna University, Bologna, Italy.
AIRC 5xMille consortium ‘Genetics-driven targeted management of lymphoid malignancies and the Italian Registry on Blastic Plasmacytoid Dendritic Cell Neoplasm

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Jennifer A. Woyach · 1985 to 2026
$132.3M
Tissue CoreP01CA081534 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KIPPS, THOMAS J · 2000 to 2016
$59.5M
TOWARD AN UNDERSTANDING OF CLL PROGRESSIONR01CA151319 · NCI · OHIO STATE UNIVERSITY · PI CROCE, CARLO M · 2011 to 2015
$1.5M
NCI NIH HHS P01 CA081534NCI NIH HHS P30 CA016058NCI NIH HHS R01 CA151319
6 · The paper itself

Abstract

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.

Indexed as

Gene Expression ProfilingCell CycleDendritic CellsHumansLeukemia, Myeloid, AcuteNF-kappa BSignal TransductionNF-kappa B

Identifiers

PMID24504027
PMCPMC4294271

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.