Proliferation of mature plasmacytoid dendritic cells in RUNX1-mutated Acute Myeloid Leukemia
Year: 2025
Type: conference-abstract
Abstract: Introduction: Clonal expansion of mature plasmacytoid dendritic cells (pDCs), traditionally linked to chronic myelomonocytic leukemia, has recently been described in acute myeloid leukemia (AML), with an estimated prevalence of 5% and associated RUNX1 mutations in over 70% of cases (Xiao, W, Blood 2021). WHO-2022 classification includes myeloid neoplasms with pDC proliferation, defined by ≥2% pDCs mesured by flow cytometry in bone marrow or peripheral blood. Our study aimed to assess the frequency of RUNX1-mutated AML (RUNX1-AML) with pDC expansion and to explore clinical, biological, and prognostic characteristics. Methods: We retrospectively analyzed 38 adults diagnosed with RUNX1-AML from 2014 to 2025. Clinical and biological baseline data were collected, and flow cytometry records were reviewed to quantify pDCs (markers: CD141, CD123, CD4, CD11c, CD117, CD203c, CD34, CD56, HLA-DR, CD45). A 2% cutoff was applied per WHO 2022 criteria, with an additional subanalysis at 0.3% (lower pDC threshold in normal bone marrow). A targeted myeloid NGS panel of 39 genes was performed with a median depth of ×1400 with Illumina platform. Results: Of 38 RUNX1-AML patients, 5 (13%) had pDCs ≥2% (pDC-AML). This group showed differences in age (median 82.1 vs 62.2 years; p=0.0056), hemoglobin (10.5 vs 8.8 g/dL; p=0.04) and platelet counts (163.6 vs 65.2 ×10⁹/L; p=0.0023). Monocytic blast differentiation was more frequent by cytology (p=0.001) and flow cytometry (p=0.047). Blasts expressed higher levels of CD123, CD64, and CD4, though differences were not statistically significant. RUNX1 variant allele frequency was higher in pDC-AML (50.7% vs 34.5%), all of them showing truncating mutations (100% vs 48%, p=0.057). Concurrent TET2 mutations were more frequent in pDC-AML (60% vs 21%, p=0.033). Due to advanced age, none of pDC-AML patients received intensive therapy. Mortality was similar between groups. Subanalysis including patients with pDC >0.3% (n=9, 23%) yielded similar results. Conclusions: pDC expansion ≥2% was observed in 13% of RUNX1-AML patients, showing differences in age, hemoglobin and platelet counts, and also, more monocytic blast differentiation. This subgroup had more truncating RUNX1 mutations and frequent co-mutations in TET2. These findings suggest that pDC expansion identifies a distinct clinical and genetic subset within RUNX1-AML.
Source: Blood
Authors: Marina Serra Carrera, Sara Garrido Paniagua, Carlos Palacio, Maria Gabarros-Subira, Maria Julia Montoro, Gloria Hidalgo-Gomez, Margarita Ortega, Silvia Saumell, Adoracion Blanco, Sergi Camarillas, Francisco Beas, Jonay Méndez, Maria Landwehr, Anna Martín Carrizosa, Sandra Novoa Jáuregui, Alba Puyuelo, Félix López Cadenas, Ana Perez Gonzalez, Olga Salamero, David Valcarcel, Andres Jerez, Laura Gallur
Institution: Vall d'Hebron Hospital Universitari
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W7108458858
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