Plasmacytoid dendritic cell neoplasms

Abstract

Plasmacytoid dendritic cells (pDCs) are type I interferon-producing cells that modulate immune responses. There are two types of pDC neoplasms: 1) mature pDC proliferation (MPDCP) associated with myeloid neoplasm and 2) blastic pDC neoplasm (BPDCN). MPDCP is a clonal expansion of mature pDCs that is predominantly associated with chronic myelomonocytic leukemia. In contrast, BPDCN is a clinically aggressive myeloid malignancy involving the skin, bone marrow, lymphatic organs, and central nervous system. There are various types of skin lesions, ranging from solitary brown or violaceous to disseminated cutaneous lesions, which often spread throughout the body. The expression of CD4, CD56, CD123, and pDC markers (TCL-1, TCF4, CD303, and CD304, etc.) are typical immunophenotype of BPDCN. Historically, BPDCN treatment has been based on acute leukemia regimens and allogeneic hematopoietic cell transplantation in selected patients. Recent advances in molecular biology and genetics have led to the development of targeted agents, such as tagraxofusp (a recombinant fusion protein targeting CD123), anti-CD123 CAR-T cells, XmAb14045, and IMGN632. Lastly, this review provides a comprehensive overview of pDC neoplasms.

Multiple Genomic Alterations, Including a Novel AFF4::IRF1 Fusion Gene, in a Treatment-Refractory Blastic Plasmacytoid Dendritic-Cell Neoplasm: A Case Report and Literature Review

“…BPDCN is more common in older men with a 3:1 to 5:1 sex ratio and a median age of diagnosis of 60 to 70 years [ 3 ]. It has an aggressive clinical course and poor prognosis with a median overall survival of 2 years [ 2 , 4 ]. It is known to be derived from the precursors of plasmacytoid dendritic cells and mostly presents with skin lesions, with or without bone marrow or extramedullary involvement [ 2 , 5 ].…”

“…Today, various treatments are available for BPDCN including chemotherapeutics, autologous and allogeneic hematopoietic stem cell transplantations, Nuclear Factor-kappa B pathway inhibitors (Bortezomib), DNA hypomethylating agents (5-Azacytidine), BCL2 inhibitors (Venetoclax), bromodomain inhibitors, folate metabolism inhibitors (Pralatrexate) and CD123 targeted therapies (Tagraxofusp) [ 12 , 13 , 15 ]. However, despite the availability of treatment options, a majority of the patients have a poor prognosis and short survival times [ 4 ]. In addition to uncertainties in the pathophysiology and biology of BPDCN, the prognostic indicators remain unclear.…”

Pathologic characteristics of histiocytic and dendritic cell neoplasms

“…Notably, CD56 may be absent, expressed at low levels, or partially expressed. The Ki-67 proliferation index is usually low, particularly when MPDCP is associated with chronic myelomonocytic leukemia [ 3 , 39 , 40 , 53 , 54 ].…”

“…Alternatively, it may express any of the three plasmacytoid dendritic cell markers in the absence of the expected negative markers of the lymphoid or myeloid lineage, such as CD3, CD14, CD19, CD34, lysozyme, and myeloperoxidase. CD34 is typically negative, and the Ki-67 proliferation index is high [1][2][3][54][55][56][57].…”

Breakthrough in Blastic Plasmacytoid Dendritic Cell Neoplasm Cancer Therapy Owing to Precision Targeting of CD123

“…The nomenclature evolved in 2016 when the World Health Organization (WHO) classified BPDCN as a distinct malignancy within myeloid neoplasms and acute leukemia [5,6]. While the specific developmental pathway of pDC malignancies remains a subject of debate, prevailing evidence supports that the malignant proliferation of pDC precursors is specifically involved in the pathogenesis of BPDCN [3,7,8]. To comprehend this, it is essential to delve into the classification of DCs and their functional subtypes.…”