Open AccessPlasmacytoid dendritic cells proliferation associated with acute myeloid leukemia: phenotype profile and mutation landscape
Author(s) -
Loria Zalmaï,
PierreJulien Viailly,
Sabeha Biichlé,
Meyling Cheok,
Lou Soret,
Fanny AngelotDelettre,
Tony Petrella,
MarieAgnès CollongeRame,
Estelle Seillès,
Sandrine Geffroy,
Eric Deconinck,
Étienne Daguindau,
Sabrina Bouyer,
Elodie Dindinaud,
Victor Baunin,
Magali Le GarffTavernier,
Damien RoosWeil,
Orianne WagnerBallon,
Véronique Salaün,
Jean Feuillard,
Sophie Brun,
Bernard Drénou,
Caroline MayeurRousse,
Patricia Okamba,
Véronique Dorvaux,
Michel Tichionni,
Johann Rose,
Marie Thérèse Rubio,
Marie Christine Jacob,
Victoria Raggueneau,
Claude Preudhomme,
Philippe Saas,
Christophe Ferrand,
Olivier Adotévi,
Christophe Roumier,
Fabrice Jardin,
Francine GarnacheOttou,
Florian Renosi
Publication year - 2020
Publication title -
haematologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.782
H-Index - 142
eISSN - 1592-8721
pISSN - 0390-6078
DOI - 10.3324/haematol.2020.253740
Subject(s) - interleukin 3 receptor , runx1 , myeloid , cd34 , myeloid leukemia , chronic myelomonocytic leukemia , phenotype , plasmacytoid dendritic cell , cancer research , leukemia , biology , immunology , immunophenotyping , gene , haematopoiesis , flow cytometry , dendritic cell , antigen , bone marrow , myelodysplastic syndromes , stem cell , genetics
Neoplasms involving plasmacytoid Dendritic Cells (pDCs) include Blastic pDC Neoplasms (BPDCN) and other pDC proliferations, where pDCs 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 pDCs in pDC-AML, and their link with the CD34+ blasts, monocytes or conventional DCs (cDCs) associated in the same sample, by phenotypic and molecular analyses (targeted NGS, 70 genes). We compared 15 pDC-AML at diagnosis with 21 BPDCN and 11 normal pDCs from healthy donors. CD45low CD34+ blasts were found in all cases (10-80% of medullar cells), associated with pDCs (4-36%), monocytes in 14 cases (1-10%) and cDCs (2 cases, 4.8-19%). pDCs 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 pre-pDC stage. In all cases, pDCs, 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 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.