The emerging role of plasmacytoid dendritic cell proliferation in acute myeloid leukemia

The mature plasmacytoid dendritic cell proliferation associated with myeloid neoplasm represents a clonal proliferation of plasmacytoid dendritic cells within myeloproliferative and myelodysplastic disorders. This entity was recently recognized as a distinct condition in the fifth edition of the World Health Organization classification of hematolymphoid tumors. It occurs in approximately 4.9% of acute myeloid leukemia cases. The pathogenic mechanisms underlying this proliferation and the role of these cells in disease progression remain poorly understood. Nevertheless, the plasmacytoid dendritic cell proliferation associated with acute myeloid leukemia is related to distinct genetic abnormalities, worse prognosis, reduced overall survival, lower sensitivity to conventional acute myeloid leukemia therapies, and an increased risk of relapse. It also displays distinct immunophenotypic features compared to other types of mature plasmacytoid dendritic cell proliferation, raising questions about its classification and diagnostic criteria. This review provides a comprehensive overview of current knowledge regarding the plasmacytoid dendritic cell proliferation associated with acute myeloid leukemia, including terminology inconsistencies; the role of plasmacytoid dendritic cells in this entity; associated genetic alterations; immunophenotypic and morphological characteristics of blasts and plasmacytoid dendritic cells; clinical outcomes and prognostic impact; and therapeutic approaches and perspectives. Synthesizing current evidence may help improve disease recognition and highlight gaps in knowledge to guide future research.