Newly-Discovered Neural Features Expand the Pathobiological Knowledge of Blastic Plasmacytoid Dendritic Cell Neoplasm

Abstract

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive hematologic malignancy originating from plasmacytoid dendritic cells (pDCs). The microRNA expression profile of BPDCN was compared to that of normal pDCs and the impact of miRNA dysregulation on the BPDCN transcriptional program was assessed. MiRNA and gene expression profiling data were integrated to obtain the BPDCN miRNA-regulatory network. The biological process mainly dysregulated by this network was predicted to be neurogenesis, a phenomenon raising growing interest in solid tumors. Neurogenesis was explored in BPDCN by querying different molecular sources (RNA sequencing, Chromatin immunoprecipitation-sequencing, and immunohistochemistry). It was shown that BPDCN cells upregulated neural mitogen genes possibly critical for tumor dissemination, expressed neuronal progenitor markers involved in cell migration, exchanged acetylcholine neurotransmitter, and overexpressed multiple neural receptors that may stimulate tumor proliferation, migration and cross-talk with the nervous system. Most neural genes upregulated in BPDCN are currently investigated as therapeutic targets.

Incidence, treatment and outcome of central nervous system relapse in adult acute lymphoblastic leukaemia patients treated front‐line with paediatric‐inspired regimens: A retrospective multicentre Campus ALL study

“…This study confirms that HSCT represents the best option to prolong survival and should be pursued as soon as possible, though further efforts are needed to prevent the risk of post‐transplant CNS relapse. Finally, efforts are currently underway to clarify if certain biologic features may be associated with a predisposing neurotropism in ALL, as already documented in blastic plasmacytoid dendritic cell neoplasms with a CNS dissemination 51 …”

“…Finally, efforts are currently underway to clarify if certain biologic features may be associated with a predisposing neurotropism in ALL, as already documented in blastic plasmacytoid dendritic cell neoplasms with a CNS dissemination. 51 …”

Unmet Clinical Needs and Management Recommendations for Blastic Plasmacytoid Dendritic Cell Neoplasm: A Consensus-based Position Paper From an Ad Hoc International Expert Panel

“… 29 Another hypothesis, as reported in a recent study by Sapienza and co-workers, based on the microRNA expression profile, suggests possible neurogenesis of the neoplastic process. 56 …”

Conventional Therapeutics in BPDCN Patients—Do They Still Have a Place in the Era of Targeted Therapies?

“…These results suggested that a systematic preventive IT chemotherapy was indicated during first-line treatment to prevent CNS relapse and thus lead to a better outcome for patients. More recently, Sapienza et al discovered new neural features by comparing 19 BPDCN patients to 4 normal pDC samples [ 58 ]. They observed 51 deregulated miRNAs in BPDCN samples that significantly influenced neurogenesis.…”