Background: Plasmacytoid dendritic cell-associated acute myeloid leukemia (pDC-AML) is an emerging, rare subtype of AML characterized by the clonal proliferation of plasmacytoid dendritic cells (pDCs) at various stages of maturation. Although infrequent, this leukemia subtype is clinically aggressive and poses significant diagnostic and therapeutic challenges.

Objective: This review synthesizes current knowledge on the immunophenotypic, genetic, and clinical features of pDC-AML, explores its prognostic implications, and compares it with the related entity blastic plasmacytoid dendritic cell neoplasm (BPDCN).

Methods: A comprehensive literature search was conducted using databases including PubMed, Scopus, and Web of Science. Studies describing the morphology, immunophenotype, cytogenetics, molecular alterations, clinical presentation, and treatment outcomes of pDC-AML were included. Data were extracted and compiled from 16 studies encompassing 231 patients.

Results: pDC-AML predominantly affects older adults (median age ~69 years) and exhibits a male predominance (~68%). It presents with diverse AML subtypes, including AML with monocytic differentiation, minimal differentiation, and secondary AML. Bone marrow pDCs range from 2.2% to 30% and exhibit variable maturation, often expressing CD123, CD303, CD304, and variably CD34 and CD117. In contrast to BPDCN, CD56 is rarely expressed, and skin or lymph node involvement is uncommon.

Genetically, pDC-AML exhibits a complex landscape. RUNX1 mutations are the most common (14–78%), possibly driving pDC lineage commitment. Additional mutations include ASXL1, DNMT3A, SRSF2, FLT3, and BCOR. Chromosomal abnormalities such as chromosome 7 deletions, trisomy 13, and MLL or CBFA rearrangements are frequently observed. Compared to BPDCN—which shows high CD56 and TCL1 expression and more frequent TET2 mutations—pDC-AML is more genetically and phenotypically heterogeneous.

Therapeutic responses are inconsistent. Treatments include induction chemotherapy, hypomethylating agents (e.g., azacytidine plus venetoclax), and allogeneic hematopoietic stem cell transplantation (allo-HSCT). Median overall survival ranges from 9.6 to 20 months, with frequent relapse even post-HSCT. Emerging therapies targeting CD123 (e.g., tagraxofusp) and immune-modulating agents are under investigation.

Conclusion: pDC-AML is a clinically aggressive and biologically distinct AML subtype defined by clonal pDC expansion, frequent RUNX1 mutations, and suboptimal responses to current therapies. Accurate diagnosis relies on integrated immunophenotypic and genetic profiling. Despite progress, patient outcomes remain poor, underscoring the need for improved classification, prognostic markers, and targeted therapeutic strategies.

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2025
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