Characteristic repartition of monocyte subsets as a diagnostic signature of chronic myelomonocytic leukemia
Menée initialement à partir d'échantillons sanguins prélevés sur 175 patients atteints d'une leucémie myélomonocytaire chronique, puis validée sur 307 patients complémentaires, cette étude française évalue les performances d'une méthode d'analyse des monocytes pour un diagnostic précis de la maladie
Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome/ myeloproliferative neoplasm whose diagnosis is currently based on the elevation of peripheral blood monocytes to more than 1.109/L, measured over at least 3 months. Diagnosis can be ambiguous, e.g. with pre-fibrotic myelofibrosis or reactive monocytosis. We set up a multi-parameter flow cytometry assay to distinguish CD14+/CD16- classical from CD14+/CD16+ intermediate and CD14low/CD16+ non-classical monocyte subsets in peripheral blood mononucleated cells and in total blood samples. Compared to healthy donors and patients with a reactive monocytosis or another hematological malignancy, CMML patients demonstrate a characteristic increase in the fraction of CD14+/CD16- cells (cut-off value, 94.0%), The associated specificity and sensitivity were 95.1% and 90.6% in the learning set (175 samples), 94.1% and 91.9% in the validation set (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 over 94.0% of total monocytes is a highly sensitive and specific diagnostic marker that rapidly and accurately distinguishes CMML from confounding diagnoses.
Blood , résumé, 2014