Plasmacytoid Dendritic Cell-Expansion in Acute Myeloid Leukemia (pDC‑AML): a Review of Clinicopathologic Features, Genetics, and Outcomes

Plasmacytoid dendritic cell–expansion in acute myeloid leukemia (pDC-AML) is an uncommon AML subset that differs from conventional AML and from blastic plasmacytoid dendritic cell neoplasm (BPDCN). This review synthesizes the clinicopathologic, immunophenotypic, cytogenetic, and molecular features of pDC-AML, highlights its outcomes, and discusses emerging therapeutic approaches, while underscoring the need for further studies to refine classification and guide therapy.

Published cohorts show that pDC-AML occurs mainly in older male adults, with CD123 and HLA-DR forming a consistent immunophenotypic backbone across both myeloblasts and pDCs. pDC-restricted markers (CD303, CD304, CD4, TCL1) are confined to the pDC compartment, whereas myeloblasts are enriched for CD34, CD117, and TdT. Cytogenetic findings are heterogeneous but often adverse, with recurrent − 7/del7q and trisomy 13. RUNX1 mutations and secondary-type co-mutations (ASXL1, DNMT3A, TET2, splicing factors) are frequent, while activating mutations such as FLT3 or NRAS are variably present. Outcomes are generally inferior compared with other AML subsets, though allogeneic transplantation can achieve durable remissions in a subset. Reports on venetoclax-based therapy show mixed outcomes, while CD123-directed therapies are being explored.

pDC-AML is emerging as a potentially higher-risk AML phenotype, with clinicopathologic and biologic features distinct from BPDCN. Early recognition, dual-compartment minimal residual disease assessment, timely transplant consideration, and referral for clinical trials are central to management. Standardized immunophenotypic criteria, integrated genomic profiling, and prospective evaluation of CD123-targeted and rational combination therapies are priorities to improve classification, risk stratification, and patient outcomes.