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Editorials
Expounding on the essence of epigenetic and genetic abnormalities in blastic plasmacytoid dendritic cell neoplasms
Lhara Lezama, Robert S. Ohgami
Stanford University, CA, USA
E-mail: ROBERT S. OHGAMI - rohgami@ohgami.org
doi:10.3324/haematol.2018.211557
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy now known to derive from immature plasmacytoid den- dritic cells. However, the cell of origin for this entity was unknown a mere two decades ago when it was alterna- tively speculated to be of natural killer (NK)-cell or mono- cytic origin. Coupled with recent advancements in genetic technologies, we have been at an inflection point in time for understanding the essence of this disease.1
The recent paper by Sapienza et al., in this issue of the Journal, makes a groundbreaking and essential push for- ward in our understanding of BPDCN.2 The work is piv- otal as: 1) it is the first to focus specifically on understand- ing epigenetic alterations in BPDCN; 2) it studies a large number of well annotated cases of BPDCN using broad and comprehensive genetic analyses; and 3) it assesses the therapeutic value of targeting BPDCN with epigenetic modifying therapies in vivo. However, to understand the importance of the study by Sapienza et al., it is critical to provide an overview of this neoplasm.
Initially described in 1990 as a possible histiocytic or monoblastic leukemia,3,4 and then later believed to be an NK-cell tumor due to expression of both CD56 and
CD4,5,6 the cellular lineage of BPDCN was debated for more than a decade. Then, in 1999, Lucio et al.7 postulated a dendritic cell origin due to expression of CD123, a sen- sitive, though not specific, plasmacytoid dendritic cell marker. Further research continued to support the plasma- cytoid dendritic cell origin based not only on CD123 expression but also expression of TCL1 and also cellular differentiation assays, all which pointed to plasmacytoid dendritic cells as the normal cellular counterpart for this tumor.8-10 In the 2008 World Health Organization classifi- cation, it was finally introduced as BPDCN and has con- tinued with this designation in the revised 2016 WHO classification. BPDCN demonstrates aggressive behavior, presenting with cutaneous lesions and bone marrow involvement, and, despite a frequent good response to ini- tial therapy, the median survival varies from 10 to 19.8 months.
The genetics and molecular aspects of this entity have also been explored by several groups. An abnormal kary- otype is common (>50% of patients) and particular chro- mosome regions are more frequently targeted in BPDCN based on classic cytogenetic analyses as well as compara- tive genomic hybridization studies: 4q, 5q, 6q, 9, 12p, 13q,
Figure 1. Genetic abnormalities and biological pathways important in blastic plasmacytoid dendritic cell neoplasm.
haematologica | 2019; 104(4)