Biology and prognostic impact of clonal plasmacytoid dendritic cells in chronic myelomonocytic leukemia

Nolwenn Lucas, Matthieu Duchmann, Philippe Rameau, Floriane Noël, Paula Michea, Véronique Saada, Olivier Kosmider, Gérard Pierron, Martin E Fernandez-Zapico, Matthew T. Howard, Rebecca King, Sandrine Niyongere, M’boyba Khadija Diop, Pierre Fenaux, Raphael Itzykson, Christophe Willekens, Vincent Ribrag, Michaela Fontenay, Eric Padron, Vassili SoumelisNathalie Droin, Mrinal M Patnaik, Eric Solary

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10 Scopus citations

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.

Original languageEnglish (US)
JournalLeukemia
DOIs
StatePublished - Jan 1 2019

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ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Lucas, N., Duchmann, M., Rameau, P., Noël, F., Michea, P., Saada, V., Kosmider, O., Pierron, G., Fernandez-Zapico, M. E., Howard, M. T., King, R., Niyongere, S., Diop, M. K., Fenaux, P., Itzykson, R., Willekens, C., Ribrag, V., Fontenay, M., Padron, E., ... Solary, E. (2019). Biology and prognostic impact of clonal plasmacytoid dendritic cells in chronic myelomonocytic leukemia. Leukemia. https://doi.org/10.1038/s41375-019-0447-3