Immunophenotypic and Molecular Features of Acute Myeloid Leukemia with Plasmacytoid Dendritic Cell Differentiation Are Distinct from Blastic Plasmacytoid Dendritic Cell Neoplasm.

Abstract

Simple SummaryAcute myeloid leukemia with plasmacytoid dendritic cell differentiation (pDC-AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN) are two leukemias characterized by neoplastic pDC proliferation. In this study, we aimed to explore the immunophenotypic and molecular profiles of pDC-AML and compare them with BPDCN. We found that pDCs in pDC-AML and BPDCN possessed different immunophenotype. The mutation profiles of these two were also different. These findings demonstrate that pDC-AML and BPDCN are two distinct entities and pDCs in these two entities derive from different subsets of pDC precursors.Acute myeloid leukemia (AML) with ≥2% plasmacytoid dendritic cells (pDC) has been recently described as AML with pDC differentiation (pDC-AML) characterized by pDC expansion with frequent RUNX1 mutations. In this study, we investigated a cohort of 53 pDC-AML cases representing about 3% of all AML cases. We characterized their immunophenotype and genetic profiles and compared these findings with blastic plasmacytoid dendritic cell neoplasm (BPDCN). pDC-differentiation/expansion was preferentially observed in AML with an immature myeloid or myelomonocytic immunophenotype, where myeloblasts were frequently positive for CD34 (98%), CD117 (94%), HLA-DR (100%) and TdT (79%), with increased CD123 (89%) expression. The median number of pDCs in pDC-AML was 6.6% (range, 2% to 26.3%) and their immunophenotype reminiscent of pDCs in early or intermediate stages of differentiation. The immunophenotype of pDCs in pDC-AML was different from BPDCN (n = 39), with major disparities in CD34 (96% vs. 0%), CD56 (8% vs. 97%) and TCL1 (12% vs. 98%) and significant differences in frequency of CD4, CD13, CD22, CD25, CD36, CD38, CD117 and CD303 expression. At the molecular level, the genetic landscapes of pDC-AML and BPDCN also differ, with RUNX1 mutations detected in 64% of pDC-AML versus 2% of BPDCN. Disparities in TET2 (21% vs. 56%), FLT3 (23% vs. 0%), DNMT3A (32% vs. 10%) and ZRSR2 (2% vs. 16%) (all p < 0.05) were also detected. The distinct immunophenotypic and mutation profiles of pDC-AML and BPDCN indicate that the neoplastic pDCs in pDC-AML and BPDCN derived from different subsets of pDC precursors.