Integrative molecular profiling identifies two molecularly and clinically distinct subtypes of blastic plasmacytoid dendritic cell neoplasm

Chronic myelomonocytic leukemia transdifferentiation landscape: From histiocytosis to blastic plasmacytoid dendritic cell neoplasm

“…Blood FCM found 0.1% of circulating abnormal BPDCN cells, marrow examination was not done. This case not only illustrates the plasticity between CMML, BPDCN, 1 and histiocytosis 2,3 but also potential therapeutic value of MEK inhibitors in combination with azacitidine in RAS ‐mutated CMML, especially in case of extra‐medullar involvement 4 …”

Genome-wide DNA methylation-analysis of blastic plasmacytoid dendritic cell neoplasm identifies distinct molecular features

“…2 ). Additionally, mutational landscape, MutSigCV analysis, and immunohistochemical profiles were extended to new cases as described (Supplementary Tables 1 , 2 , and 3 ) [ 6 ]. Tumor mutational burden (TMB) was confirmed to be significantly higher ( p = 0.0055) among C1-BPDCN and the set of differentially mutated genes was updated (Supplementary Fig.…”

“…In one case, we observed the simultaneous occurrence of typical BPDCN and pDC-AML infiltrates, the latter seemingly emerging from an underlying MDS. Moreover, all but one of these cases exhibit the more immature C2-BPDCN transcriptional profile [ 6 ]. This aligns with observations in B-cell malignancies and solid tumors where the DNA methylation profile reflects the degree of maturation of the cell-of-origin [ 32 , 43 ].…”

“…In this study, we have extended our previously published BPDCN cohort [ 6 ], assessed by paired whole-exome (WES) and transcriptome sequencing (RNA-seq) as well as genome-wide copy number analysis and conducted array-based genome-wide DNA methylation profiling and ATAC-sequencing on selected cases, allowing for a more profound and novel understanding of BPDCN pathobiology and reliable discrimination from AML as the predominant diagnostic challenge in clinical practice. Moreover, we identify two immunological subtypes, characterized by features in the TME and recurrent genomic alterations.…”

Genome-wide DNA methylation-analysis delineates blastic plasmacytoid dendritic cell neoplasm from related entities and identifies distinct molecular features

“…In its recent editions, the WHO classification of myeloid neoplasms recognizes BPDCN as a distinct entity descending from non-activated, CD56 + plasmacytoid dendritic cells (pDC) 1,2,3 . However, a broader cellular origin encompassing transcriptional signatures of both AXL1 + SIGLEC6 + DCs and earlier, common dendritic cells, termed AS-DCs and cDCs, respectively, has been proposed, before, suggesting a diverse cellular ontogeny 4,5,6 . Clinically, skin lesions commonly precede bone marrow infiltration and secondary propagation into lymph nodes and extranodal organs.…”