The Plasmacytoid Dendritic Cell CD123+ Compartment in Acute Leukemia with or without RUNX1 Mutation: High Inter-Patient Variability Disclosed by Immunophenotypic Unsupervised Analysis and Clustering

Abstract

Plasmacytoid dendritic cells (PDC) constitute a small subset of normal bone marrow (BM) cells but have also been shown to be present, sometimes in large numbers, in several hematological malignancies such as acute myeloid leukemia with RUNX1 mutation, chronic myelomonocytic leukemia or, obviously, blastic plasmacytoid dendritic cell neoplasms. These cells have been reported to display somewhat variable immunophenotypic features in different conditions. However, little is known of their plasticity within individual patients. Using an unsupervised clustering tool (FlowSOM) to re-visit flow cytometry results of seven previously analyzed cases of hematological malignancies (6 acute myeloid leukemia and one chronic myelomonocytic leukemia) with a PDC contingent, we report here on the unexpectedly high variability of PDC subsets. Although five of the studied patients harbored a RUNX1 mutation, no consistent feature of PDCs could be disclosed as associated with this variant. Moreover, the one normal single-node small subset of PDC detected in the merged file of six normal BM could be retrieved in the remission BM samples of three successfully treated patients. This study highlights the capacity of unsupervised flow cytometry analysis to delineate cell subsets not detectable with classical supervised tools.

Mixed Phenotype/Lineage Leukemia: Has Anything Changed for 2021 on Diagnosis, Classification, and Treatment?

“…The latter has been developed in the R Bioconductor environment for a fast hierarchical clustering of cell subsets with shared immunophenotypic features [ 7 •, 35 •]. Our group has published on the use of this tool for the detection of minimal residual disease in AML [ 36 •], to characterize blastic plasmacytoid dendritic cells neoplasms (BPDCN) [ 37 ], to investigate erythroid differentiation in normal bone marrow [ 38 ] and in patients with clonal or non-clonal anemia [ 39 ]. We recently selected 10 normal bone marrow (NBM) samples analyzed with an MPAL-oriented panel (Fig.…”