Molecular Features of Blastic Plasmacytoid Dendritic Cell Neoplasm

Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with poor outcome. BPDCN diagnostically overlaps with entities such as acute myeloid leukemia, histiocytic/dendritic cell neoplasms, and NK/T cell lymphomas. Unfortunately, large patient centered studies that comprehensively analyze clinical, pathologic and other diagnostic features are lacking. As such, there is an incomplete understanding of this disease. To better characterize BPDCN, a multicenter working group consisting of hematopathologists and dermatopathologists gathered in-person and remotely to review the current understanding of BPDCN, discuss specific issues regarding the diagnosis and differential diagnosis, and perform a retrospective analysis of the literature. A curated database of published BPDCN patient cases (BPDCN Network literature database) was generated. By conducting an in-depth analysis, not only did we confirm known findings in BPDCN such as frequent skin involvement and male predominance amongst older patients, but we also identified a number of under-recognized features, such as significant central nervous system involvement (35% of cases), and a roughly equal female to male prevalence amongst patients < 40 years old. Furthermore, with the large database, we were able to accurately summarize the immunohistochemical, cytogenetic, and molecular features of this disease. The BPDCN Network literature database serves as a central data repository of archived published aggregated and individual cases and facilitates an in-depth characterization of this rare disease. Continual updates from the consortium and beyond will allow for prospective refinement of our understanding of this orphan disease. Disclosures Ohgami: Stemline Therapeutics: Research Funding. Aung: Stemeline Therapeutics: Honoraria. Gru: Innate Pharma: Research Funding; StemLine: Honoraria, Research Funding, Speakers Bureau; CRISPT Therapeutics: Research Funding. Hussaini: Stemeline Therapeutics: Honoraria. Jaye: Stemline Therapeutics: Honoraria. Wang: Stemline Therapeutics: Honoraria. Pullarkat: Stemline Therapeutics: Honoraria. George: Bristol Meyers Squibb: Consultancy; Incyte Corporation: Consultancy; Blueprint Medicines: Consultancy; Celgene: Consultancy.

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Features of non-activation dendritic state and immune deficiency in blastic plasmacytoid dendritic cell neoplasm (BPDCN)

Blood Cancer Journal ◽

10.1038/s41408-019-0262-0 ◽

2019 ◽

Vol 9 (12) ◽

Cited By ~ 3

Author(s):

Hannah C. Beird ◽

Maliha Khan ◽

Feng Wang ◽

Mansour Alfayez ◽

Tianyu Cai ◽

...

Keyword(s):

Bone Marrow ◽

Dendritic Cell ◽

Peripheral Blood ◽

Profile Analysis ◽

Hematologic Malignancy ◽

Plasmacytoid Dendritic Cell ◽

Serum Samples ◽

Molecular Features ◽

Cell Neoplasm ◽

Poor Outcomes

AbstractBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, male-predominant hematologic malignancy with poor outcomes and with just one recently approved agent (tagraxofusp). It is characterized by the abnormal proliferation of precursor plasmacytoid dendritic cells (pDCs) with morphologic and molecular similarities to acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)/chronic myelomonocytic leukemia (CMML) in its presentation within the bone marrow and peripheral blood. To identify disease-specific molecular features of BPDCN, we profiled the bone marrow, peripheral blood, and serum samples from primary patient samples using an in-house hematologic malignancy panel (“T300” panel), transcriptome microarray, and serum multiplex immunoassays. TET2 mutations (5/8, 63%) were the most prevalent in our cohort. Using the transcriptome microarray, genes specific to pDCs (LAMP5, CCDC50) were more highly expressed in BPDCN than in AML specimens. Finally, the serum cytokine profile analysis showed significantly elevated levels of eosinophil chemoattractants eotaxin and RANTES in BPDCN as compared with AML. Along with the high levels of PTPRS and dendritic nature of the tumor cells, these findings suggest a possible pre-inflammatory context of this disease, in which BPDCN features nonactivated pDCs.

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Blastic plasmacytoid dendritic cell neoplasm

Pediatric Hematology/Oncology and Immunopathology ◽

10.24287/1726-1708-2019-18-4-79-89 ◽

2019 ◽

Vol 18 (4) ◽

pp. 79-89

Author(s):

T. T. Valiev ◽

G. Z. Seregin ◽

I. N. Serebryakova ◽

O. A. Chernyshova ◽

N. A. Kupryshina ◽

...

Keyword(s):

Dendritic Cell ◽

Hematologic Malignancy ◽

Lymphoblastic Leukemia ◽

Plasmacytoid Dendritic Cell ◽

Molecular Genetic ◽

Allogeneic Bone Marrow Transplantation ◽

Clinical Analysis ◽

Allogeneic Bone ◽

Molecular Features ◽

Cell Neoplasm

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare hematologic malignancy. Our view of the cellular origins of this kind of tumor has been changing dramatically with the emergence of new data on the molecular biological and immunological characteristics of the tumor. This article discusses the clinical features of BPDCN, as well as the cytological, morphological-immunological and molecular genetic criteria for BPDCN diagnosis. Taking into account the rare incidence of BPDCN, as well as its rather complex diagnostic procedure, which requires an extended diagnostic antibody panel, standard methods of therapy have not been developed. Chemotherapy protocols for acute lymphoblastic leukemia and acute myeloid leukemia are used, with/without subsequent autologous/allogeneic bone marrow transplantation, but the results remain unsatisfactory. For the first time in Russian cancer research, this article provides a description of BPDCN in a 14-year-old child. A detailed clinical analysis of this rare tumor is provided, as well as dermatoscopy results and a description of the histological, immunological and molecular features of BPDCN, from the point of view of differential diagnosis. Parents patients agreed to use personal data in research and publications.

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