BPDCN, AML with PDC Differentiation Have Distinct Immunophenotypes, Mutations

Acute myeloid leukemia (AML) with plasmacytoid dendritic cell (PDC) differentiation and blastic plasmacytoid dendritic cell neoplasm (BPDCN) have distinct immunophenotypic and mutation profiles, according to a recent study.

Wei Wang, MD, PhD, of the University of Texas MD Anderson Cancer Center, and colleagues conducted the study and published its results in Cancers.

The researchers investigated a cohort of patients who had AML with PDC differentiation (n=53) and compared their immunophenotypic and genetic profiles with those from patients with BPDCN (n=39).

PDC differentiation and expansion was “preferentially observed” in patients who had AML with an immature myeloid or myelomonocytic immunophenotype, the researchers reported. In these patients, myeloblasts were often positive for CD34 (98%), CD117 (94%), HLA-DR (100%), and TdT (79%) and had increased CD123 expression (89%). The median percentage of PDCs was 6.6% (range, 2-26.3%) in these patients.

“The immunophenotype [was] reminiscent of [plasmacytoid dendritic cells] in early or intermediate stages of differentiation,” the researchers wrote.

There were key differences in the immunophenotypes of PDCs between the disease states. Most PDCs from patients who had AML with PDC differentiation (96%) were positive for CD34, while none of the PDCs from patients with BPDCN were positive for CD34 (P<.0001). Conversely, most PDCs from patients with BPDCD (97%) expressed CD56, while it was only detected in 8% of PDCs from patients with AML with PDC differentiation (P<.0001). There also were significant differences between disease states in the frequency of TCL1, CD4, CD13, CD22, CD25, CD36, CD38, CD117, and CD303 expression in PDCs.

RUNX1 mutations were detected in significantly more patients who had AML with PDC differentiation (64%) than in patients with BPDCN (2%; P<.0001). FLT3 mutations were reported in 23% of patients who had AML with PDC differentiation but none of the patients with BPDCN (P=.0003). DNMT3A mutations were also more common in AML with PDC differentiation (32%) than in BPDCN (10%; P=.0079). However, mutations in TET2 were more common in patients with BPDCN (56%) than in patients who had AML with PDC differentiation (21%; P=.0003), as were ZRSR2 mutations (16% and 2%, respectively; P=.03).

“The distinct immunophenotypic and mutation profiles of [AML with PDC differentiation] and BPDCN indicate that the neoplastic PDCs in [AML with PDC differentiation] and BPDCN derived from different subsets of PDC precursors,” Dr. Wang and colleagues concluded.

Wang W, Xu J, Khoury JD, et al. Immunophenotypic and molecular features of acute myeloid leukemia with plasmacytoid dendritic cell differentiation are distinct from blastic plasmacytoid dendritic cell neoplasm. Cancers (Basel). 2022;14(14):3375.