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Characteristic repartition of monocyte subsets as a diagnostic signature of chronic myelomonocytic leukemia

Dorothée Selimoglu-Buet, Orianne Wagner-Ballon, Véronique Saada, Valérie Bardet, Raphaël Itzykson, Laura Bencheikh, Margot Morabito, Elisabeth Met, Camille Debord, Emmanuel Benayoun, Anne-Marie Nloga, Pierre Fenaux, Thorsten Braun, Christophe Willekens, Bruno Quesnel, Lionel Adès, Michaela Fontenay, Philippe Rameau, Nathalie Droin, Serge Koscielny and Eric Solary on behalf of the Groupe Francophone des Myélodysplasies

Key Points

  • An increase in the classical monocyte subset to >94% of total monocytes discriminates CMML from other monocytoses with high specificity.

  • This characteristic increase in classical monocytes disappears in CMML patients who respond to hypomethylating agents.

Abstract

Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome/ myeloproliferative neoplasm whose diagnosis is currently based on the elevation of peripheral blood monocytes to >1 × 109/L, measured for ≥3 months. Diagnosis can be ambiguous; for example, with prefibrotic myelofibrosis or reactive monocytosis. We set up a multiparameter flow cytometry assay to distinguish CD14+/CD16 classical from CD14+/CD16+ intermediate and CD14low/CD16+ nonclassical monocyte subsets in peripheral blood mononucleated cells and in total blood samples. Compared with healthy donors and patients with reactive monocytosis or another hematologic malignancy, CMML patients demonstrate a characteristic increase in the fraction of CD14+/CD16 cells (cutoff value, 94.0%). The associated specificity and sensitivity values were 95.1% and 90.6% in the learning cohort (175 samples) and 94.1% and 91.9% in the validation cohort (307 samples), respectively. The accumulation of classical monocytes, which demonstrate a distinct gene expression pattern, is independent of the mutational background. Importantly, this increase disappears in patients who respond to hypomethylating agents. We conclude that an increase in the fraction of classical monocytes to >94.0% of total monocytes is a highly sensitive and specific diagnostic marker that rapidly and accurately distinguishes CMML from confounding diagnoses.

  • Submitted January 6, 2015.
  • Accepted March 31, 2015.
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