Blastic Dendritic Cell Neoplasms (BPDCNs) and AML Associated with an Excess of pDC (AML-pDC)

Dear Colleagues,

In recent years, new insights into two types of neoplastic counterparts for plasmacytoid dendritic cells (pDCs) have been obtained. The first is blastic pDC neoplasm (BPDCN), and the second is acute myeloid leukemia (AML) associated with an excess of pDCs, called pDC-AML (to be related to mature pDC proliferation (MPDCP) associated with a myeloid neoplasm in the WHO 2017 classification).

These two malignancies, presenting mostly as acute leukemia, are rare and probably underdiagnosed. Diagnosis is still challenging because of their rarity, the absence of specific cytogenetic or molecular markers, some similarities with other leukemias (particularly AML), and because the differential diagnosis between these two proliferations emerged only recently. Indeed, recommendations for mandatory criteria to diagnose these two proliferations is clearly needed.The normal counterpart of BPDCN is considered to belong to the pDC lineage. However, recent advances in HLA-DR⁺ CD123⁺ DCs with the description of canonical pDCs and AS-DCs highlight the complexity of pDC ontogeny. Data clarifying the exact progenitor involved in BPDCN and in pDC-AML are still needed, and would be of interest to better understand these leukemias, their similarities and differences.

The mutational landscape of BPDCN emerged as very complex, with some similarities with AML (high frequency of TET2, ASXL1, and ZRSR2 for example) associated with “lymphoid-like” defects (targeting namely IKZF1, CDKN2A/B, MYC). Chromosomal losses are frequent, invalidating many key genes (RB1, ETV6; IKZF1, NR3C1). Interestingly, rearrangements of MYC and MYB implying their upregulation have been described in recent years in a part of patients, while various pathways are deregulated in BPDCN, notably NF-κB pathway, cholesterol and corticosteroid metabolism. Some of these studies have already uncovered oncogenic pathways implicated in BPDCN in order to develop potential therapeutic targets in this aggressive leukemia. Lately, a miRNA-specific profile of BPDCN has been described, compared to myeloid sarcoma. Conversely, the genomic profile of pDC-AML is poorly understood, even if a clonal relationship between pDCs and the associated myeloid blasts is now clearly proven. Mutations of RUNX1 are clearly prevalent in these AML-pDCs, particularly in cases with very immature blastic cells (classified as AML-0 in the FAB classification). AML with mutated RUNX1 constitute a provisional entity in the WHO 2017 classification. The relationship between RUNX1 mutations and clonal pDCs in AML is still to be investigated.

BPDCN and pDC-AML are both aggressive. For this reason, the development of new therapeutic strategies, the identification of prognostic factors and the determination of MRD criteria, useful for patient monitoring, are mandatory in light of their high rate of relapse. C123 is expressed in 100% of BPDCN and frequent in pDC-AML, but at a lower level. Many therapies can target CD123, but their management in terms of sequence, combinations with other drugs, or with allograft is not clearly determined in BPDCN since relapse still occurred after CD123 targeted therapies. Their interest in pDC-AML remains to be determined and we still have little data on therapies targeting oncogenic pathways that might be evaluated in models of these neoplasms.

This Special Issue will highlight the above mentioned topics, including progenitors leading to BPDCN and pDC-AML, the oncogenic dysregulation revealed by functional studies and the relationship between these two entites. A better future for patients with BPDCN is foreseen, using early CD123 targeting therapy alone or in combination with targeted agents (e.g., DNA methylation inhibitors, histone deacetylase inhibitors, BH3-mimetics, or others).

Prof. Dr. Francine Garnache Ottou
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• BPDCN
• MPDCP
• AML-pDC
• diagnosis
• treatment
• IL3 receptor alpha (CD123)
• CAR T cells