Clinical Insights into the Management of Blastic Plasmacytoid Dendritic Cell Neoplasm

Zhang, Yumeng; Sokol, Lubomir

doi:10.2147/cmar.s330398

Cited by 5 publications

(3 citation statements)

References 82 publications

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“…The FDA approved tagraxofusp (SL-401), a CD123-directed cytotoxin, containing human interleukin-3 fused to truncated diphtheria toxin, for adults and pediatric patients older than 2 years who have either treatment-naïve or relapsed/refractory BPDCN. 9 An open-label, multi-cohort study with 47 patients with untreated or relapsed BPDCN recruited, evaluated the efficacy of intravenous injection of tagraxofusp at a dose of 7 μg or 12 μg per kilogram of body weight on days 1 to 5 of each 21-day, with over 90% overall response rate. 10 …”

Section: Discussionmentioning

confidence: 99%

Blastic Plasmacytoid Dendritic Cell Neoplasm with Lung Involvement and Cytopenia: A Case Report and a Literature Review

Liu¹,

Qi²,

Zhang³

et al. 2023

CCID

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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a hostile cutaneous malignancy with dismal prognosis and unknown etiology with rarity. Most patients received traditional chemotherapy only has one year of median survival time. This article reports an 81-year-old male patient with BPDCN who presented with skin manifestations and was diagnosed with positive CD4, CD56, and CD123 immunohistochemical results. Systematic examination revealed lung involvement and cytopenia.

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Section: Discussionmentioning

confidence: 99%

Blastic Plasmacytoid Dendritic Cell Neoplasm with Lung Involvement and Cytopenia: A Case Report and a Literature Review

Liu¹,

Qi²,

Zhang³

et al. 2023

CCID

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“…Of these patients, nine received more than three IT sessions [19,26]. A study by Zhang et al corroborates these findings, and investigators have implemented protocol of alternating methotrexate and cytarabine IT for patients, with ongoing assessment of its efficacy [34].…”

Section: Methotrexate and Cytarabine Itmentioning

confidence: 92%

Blastic Plasmacytoid Dendritic Cell Neoplasm: A Comprehensive Review of the Disease, Central Nervous System Presentations, and Treatment Strategies

Mehra,

Taylor

2024

Cells

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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive hematologic malignancy with poor outcomes. The World Health Organization (WHO) redefined BDCN as a distinct disease entity in 2016. BPDCN arises from plasmacytoid dendritic cells, manifesting primarily in the skin, bone marrow, and lymph nodes, occasionally involving the central nervous system (CNS). This presents challenges in diagnosis and treatment, with CNS involvement often overlooked in standard diagnostic workups due to BPDCN’s rarity and patients often being neurologically asymptomatic at diagnosis. CNS involvement typically emerges during relapse, yet clinical trials often exclude such cases, limiting our understanding of its development and treatment. Treatment options for CNS involvement include intrathecal (IT) chemotherapies like methotrexate and cytarabine, often in combination with systemic agents. Tagraxofusp and traditional regimens for acute myeloid leukemia show limited success at preventing CNS relapse, prompting exploration of combined therapies like hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HyperCVAD) with venetoclax and adding IT chemotherapy to other backbones. Ongoing clinical trials investigating emerging therapies offer hope despite limited focus on CNS implications. Trials incorporating CNS-involved patients aim to pioneer novel treatment approaches, potentially reshaping BPDCN management. Understanding CNS involvement’s complexities in BPDCN remains crucial for tailored treatments and better patient outcomes.

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“…The clinical manifestations of BPDCN are predominant cutaneous involvement with subsequent or simultaneous extension to the bone marrow and peripheral blood while normal pDCs are absent from the skin. The clinical course of BPDCN patients is almost invariably aggressive and fatal [ 24 , 25 ]. At present, there is no consensus on the optimal treatment of this disease, highlighting the urgency of identifying novel therapeutic options.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional Landscape of CUT-Class Homeobox Genes in Blastic Plasmacytoid Dendritic Cell Neoplasm

Nagel,

Rand,

Pommerenke

et al. 2024

IJMS

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Homeobox genes encode developmental transcription factors regulating tissue-specific differentiation processes and drive cancerogenesis when deregulated. Dendritic cells (DCs) are myeloid immune cells occurring as two types, either conventional or plasmacytoid DCs. Recently, we showed that the expression of NKL-subclass homeobox gene VENTX is restricted to conventional DCs, regulating developmental genes. Here, we identified and investigated homeobox genes specifically expressed in plasmacytoid DCs (pDCs) and derived blastic plasmacytoid dendritic cell neoplasm (BPDCN). We analyzed gene expression data, performed RQ-PCR, protein analyses by Western blot and immuno-cytology, siRNA-mediated knockdown assays and subsequent RNA-sequencing and live-cell imaging. Screening of public gene expression data revealed restricted activity of the CUT-class homeobox gene CUX2 in pDCs. An extended analysis of this homeobox gene class in myelopoiesis showed that additional CUX2 activity was restricted to myeloid progenitors, while BPDCN patients aberrantly expressed ONECUT2, which remained silent in the complete myeloid compartment. ONECUT2 expressing BPDCN cell line CAL-1 served as a model to investigate its regulation and oncogenic activity. The ONECUT2 locus at 18q21 was duplicated and activated by IRF4, AUTS2 and TNF-signaling and repressed by BMP4-, TGFb- and IL13-signalling. Functional analyses of ONECUT2 revealed the inhibition of pDC differentiation and of CDKN1C and CASP1 expression, while SMAD3 and EPAS1 were activated. EPAS1 in turn enhanced survival under hypoxic conditions which thus may support dendritic tumor cells residing in hypoxic skin lesions. Collectively, we revealed physiological and aberrant activities of CUT-class homeobox genes in myelopoiesis including pDCs and in BPDCN, respectively. Our data may aid in the diagnosis of BPDCN patients and reveal novel therapeutic targets for this fatal malignancy.

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Clinical Insights into the Management of Blastic Plasmacytoid Dendritic Cell Neoplasm

Cited by 5 publications

References 82 publications

Blastic Plasmacytoid Dendritic Cell Neoplasm with Lung Involvement and Cytopenia: A Case Report and a Literature Review

Blastic Plasmacytoid Dendritic Cell Neoplasm with Lung Involvement and Cytopenia: A Case Report and a Literature Review

Blastic Plasmacytoid Dendritic Cell Neoplasm: A Comprehensive Review of the Disease, Central Nervous System Presentations, and Treatment Strategies

Transcriptional Landscape of CUT-Class Homeobox Genes in Blastic Plasmacytoid Dendritic Cell Neoplasm

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