Abstract
Chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative neoplasm, characterized by persistent monocytosis and dysplasia in at least one myeloid cell lineage. This persistent monocytosis should be distinguished from the reactive monocytosis which is sometimes observed in a context of infections or solid tumors. In 2015, Selimoglu-Buet et al. observed an increased percentage of classical monocytes (CD14+/CD16− >94%) in the peripheral blood (PB) of CMML patients. In this study, using multiparametric flow cytometry (MFC), we assessed the monocytic distribution in PB samples and in bone marrow aspirates from 63 patients with monocytosis or CMML suspicion, and in seven follow-up blood samples from CMML patients treated with hypomethylating agents (HMA). A control group of 12 healthy age-matched donors was evaluated in parallel in order to validate the analysis template. The CMML diagnosis was established in 15 cases in correlation with other clinical manifestations and biological tests. The MFC test for the evaluation of the repartition of monocyte subsets, as previously described by Selimoglu-Buet et al. showed a specificity of 97% in blood and 100% in marrow samples. Additional information regarding the expression of intermediate MO2 monocytes percentage improved the specificity to 100% in blood samples allowing the screening of abnormal monocytosis. The indicative thresholds of CMML monocytosis were different in PB compared to BM samples (classical monocytes >95% for PB and >93% for BM). A decrease of monocyte levels in PB and BM, along with a normalization of monocytes distribution, was observed after treatment in 4/7 CMML patients with favorable evolution. No significant changes were observed in 3/7 patients who did not respond to HMA therapy and also presented unfavorable molecular prognostic factors at diagnosis (ASXL1, TET2, and IDH2 mutations). Considering its simplicity and robustness, the monocyte subsets evaluation by MFC provides relevant information for CMML diagnosis.
Highlights
Chronic myelomonocytic leukemia (Chronic myelomonocytic leukemia) is a clonal malignant hematological disorder characterized by monocytosis and myeloid dysplastic features [1]
The aim of this study was to evaluate by multiparametric flow cytometry (MFC), the monocyte subsets, using Selimoglu-Buet test in patients showing peripheral blood (PB) monocytosis and clinical suspicion of Chronic myelomonocytic leukemia (CMML) compared to “healthy” subjects and to patients carrying other hematological diseases, in order to validate this test for routine practices
The exhaustive studies evaluating bone marrow (BM) myeloblasts, monocytes, and granulocytes showed the existence of multiple MFC abnormalities in myeloid compartments in CMML, which are closer to MDS than MPN, and unspecific for CMML [5, 16]
Summary
Chronic myelomonocytic leukemia (Chronic myelomonocytic leukemia) is a clonal malignant hematological disorder characterized by monocytosis and myeloid dysplastic features [1]. It may be difficult to discriminate CMML from reactive monocytosis (>1 × 109/L) or prefibrotic myelofibrosis using only these criteria For these reasons, multiparametric flow cytometry (MFC) was tested to evaluate the phenotypic profile in bone marrow (BM) or blood samples to find specific changes related to CMML. The study conducted by Shen et al in 118 CMML patients, promotes integration of MFC data with other clinical and biological tools in the diagnosis of CMML [5]. They evaluated all myeloid compartments (immature and mature) in BM aspirates and found alterations in granulocytic maturation in more than two-thirds of CMML patients [5]. The authors observed that immunophenotypic changes in monocytes, using the criteria established by International Workshops from the European LeukemiaNet Working Group, are not specific for CMML or other MDS settings, but make the neoplastic process visible if present [5]
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