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Comment
. 2021 Mar 11;137(10):1277-1278.
doi: 10.1182/blood.2020008745.

Targeting the p-D-C: easy as C-D-1-2-3?

Naveen Pemmaraju  1
Affiliations
Comment

Targeting the p-D-C: easy as C-D-1-2-3?

Naveen Pemmaraju. Blood. .

Abstract

In this issue of Blood, Xiao et al have reliably defined a previously elusive entity, that of blastic plasmacytoid dendritic cell neoplasm (BPDCN)-like acute myeloid leukemia (AML), or pDC-AML, which occurs in ∼5% of AML cases. Remarkably, in the vast majority of cases, pDC-AML is associated with occurrence of somatic mutations of RUNX1.

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Conflict of interest statement

Conflict-of-interest disclosure: The author reports consulting/honorarium from Celgene, Stemline, Incyte, Novartis, MustangBio, Roche Diagnostics, LFB, Pacylex, Blueprint Medicines, and Abbvie; and research funding/clinical trials support from Stemline, Novartis, Abbvie, Samus, Cellectis, Plexxikon, Daiichi-Sankyo, Affymetrix, and SagerStrong Foundation.

Conflict-of-interest disclosure: The author reports consulting/honorarium from Celgene, Stemline, Incyte, Novartis, MustangBio, Roche Diagnostics, LFB, Pacylex, Blueprint Medicines, and Abbvie; and research funding/clinical trials support from Stemline, Novartis, Abbvie, Samus, Cellectis, Plexxikon, Daiichi-Sankyo, Affymetrix, and SagerStrong Foundation.

Figures

None
AML with pDC expansion, or pDC-AML, is associated with RUNX1 mutations in the vast majority of cases (∼70%). Xiao et al demonstrate that blasts from pDC-AML that harbor RUNX1 mutations may acquire an interferon-driven pDC transcriptional program, thereby leading to increased pDCs. pDCs are known to express/overexpress CD123, or IL3Rα, which can uniquely be targeted by CD123-directed therapy. Tagraxofusp (SL-401, DT-IL3) is the first approved agent targeting CD123 (BPDCN, age ≥2 years, December 2018), opening up the possibility of novel avenues for therapeutic investigation. Figure by N. Pemmaraju.
See this image and copyright information in PMC

Comment on

References

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