Plasmacytoid dendritic cells proliferation associated with acute myeloid leukemia: phenotype profile and mutation landscape

Autor: Loria Zalmaï, Pierre-Julien Viailly, Sabeha Biichle, Meyling Cheok, Lou Soret, Fanny Angelot-Delettre, Tony Petrella, Marie-Agnès Collonge-Rame, Estelle Seilles, Sandrine Geffroy, Eric Deconinck, Etienne Daguindau, Sabrina Bouyer, Elodie Dindinaud, Victor Baunin, Magali Le Garff-Tavernier, Damien Roos-Weil, Orianne Wagner-Ballon, Véronique Salaun, Jean Feuillard, Sophie Brun, Bernard Drenou, Caroline Mayeur-Rousse, Patricia Okamba, Véronique Dorvaux, Michel Tichionni, Johann Rose, Marie Thérèse Rubio, Marie Christine Jacob, Victoria Raggueneau, Claude Preudhomme, Philippe Saas, Christophe Ferrand, Olivier Adotevi, Christophe Roumier, Fabrice Jardin, Francine Garnache-Ottou, Florian Renosi
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Haematologica, Vol 106, Iss 12 (2020)
Druh dokumentu: article
ISSN: 0390-6078
1592-8721
DOI: 10.3324/haematol.2020.253740
Popis: Neoplasms involving plasmacytoid dendritic cells (pDC) include blastic pDC neoplasms (BPDCN) and other pDC proliferations, where pDC are associated with myeloid malignancies: most frequently chronic myelomonocytic leukemia (CMML) but also acute myeloid leukemia (AML), hereafter named pDC-AML. We aimed to determine the reactive or neoplastic origin of pDC in pDC-AML, and their link with the CD34+ blasts, monocytes or conventional DC (cDC) associated in the same sample, by phenotypic and molecular analyses (targeted next-generation sequencing, 70 genes). We compared 15 pDCAML at diagnosis with 21 BPDCN and 11 normal pDC from healthy donors. CD45low CD34+ blasts were found in all cases (10-80% of medullar cells), associated with pDC (4-36%), monocytes in 14 cases (1-10%) and cDC (two cases, 4.8-19%). pDC in pDC-AML harbor a clearly different phenotype from BPDCN: CD4+ CD56– in 100% of cases, most frequently CD303+, CD304+ and CD34+; lower expression of cTCL1 and CD123 with isolated lymphoid markers (CD22/CD7/CD5) in some cases, suggesting a prepDC stage. In all cases, pDC, monocytes and cDC are neoplastic since they harbor the same mutations as CD34+ blasts. RUNX1 is the most commonly mutated gene: detected in all AML with minimal differentiation (M0-AML) but not in the other cases. Despite the low number of cases, the systematic association between M0-AML, RUNX1 mutations and an excess of pDC is puzzling. Further evaluation in a larger cohort is required to confirm RUNX1 mutations in pDC-AML with minimal differentiation and to investigate whether it represents a proliferation of blasts with macrophage and DC progenitor potential.
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