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 L. 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

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Islands of CD123high 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)
Pages (from-to)2466-2480
Number of pages15
JournalLeukemia
Volume33
Issue number10
DOIs
StatePublished - Oct 1 2019

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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