1. Biology and prognostic impact of clonal plasmacytoid dendritic cells in chronic myelomonocytic leukemia.
- Author
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Lucas N, Duchmann M, Rameau P, Noël F, Michea P, Saada V, Kosmider O, Pierron G, Fernandez-Zapico ME, Howard MT, King RL, Niyongere S, Diop MK, Fenaux P, Itzykson R, Willekens C, Ribrag V, Fontenay M, Padron E, Soumelis V, Droin N, Patnaik MM, and Solary E
- Subjects
- Aged, Aged, 80 and over, Antigens, CD metabolism, Biomarkers metabolism, Bone Marrow metabolism, Bone Marrow pathology, Dendritic Cells metabolism, Female, Humans, Leukemia, Myelomonocytic, Chronic metabolism, Male, Membrane Proteins metabolism, Prognosis, T-Lymphocytes, Regulatory metabolism, T-Lymphocytes, Regulatory pathology, Dendritic Cells pathology, Leukemia, Myelomonocytic, Chronic pathology
- Abstract
Islands of CD123
high cells have been commonly described in the bone marrow of patients with chronic myelomonocytic leukemia (CMML). Using a multiparameter flow cytometry assay, we detected an excess of CD123+ mononucleated cells that are lineage-negative, CD45+ , CD11c- , CD33- , HLA-DR+ , BDCA-2+ , BDCA-4+ in the bone marrow of 32/159 (20%) patients. Conventional and electron microscopy, flow cytometry detection of cell surface markers, gene expression analyses, and the ability to synthesize interferon alpha in response to Toll-like receptor agonists identified these cells as bona fide plasmacytoid dendritic cells (pDCs). Whole-exome sequencing of sorted monocytes and pDCs identified somatic mutations in genes of the oncogenic RAS pathway in the two cell types of every patient. CD34+ cells could generate high amount of pDCs in the absence of FMS-like tyrosine kinase 3-ligand (FLT3L). Finally, an excess of pDCs correlates with regulatory T cell accumulation and an increased risk of acute leukemia transformation. These results demonstrate the FLT3L-independent accumulation of clonal pDCs in the bone marrow of CMML patients with mutations affecting the RAS pathway, which is associated with a higher risk of disease progression.- Published
- 2019
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