Myeloid Nuclear Differentiation Antigen as a Diagnostic Marker for Myelodysplastic Syndrome using Multiparametric Flow Cytometry
Soh, Kah Teong
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Background: Myelodysplastic syndrome (MDS) is a set of clonal marrow disorders that are difficult to diagnose due to the lack of standard diagnostic parameters, admixture of normal marrow cells and paucicellularity. The expression of myeloid nuclear differentiation antigen (MNDA) was reported to be lower in MDS patients. Therefore, the evaluation of MNDA may help improve the detection of MDS. Methods: Using multiparametric flow cytometry, the expression of MNDA was compared in 101 remnant bone marrow samples, which can be categorized into: (1) patients with disease-free bone marrow, (2) patients with bone marrow diseases unrelated to MDS or acute myeloid leukemia (AML), (3) MDS patients, and (4) AML patients. These bone marrow cells were surface labeled with fluorochromone conjugated monoclonal antibodies, followed by fixation and permeabilization, and intracellularly labeled with FITC conjugated anti-MNDA (clone 3C1). Myeloid subsets with diminished MNDA expression were identified using a gating strategy that distinguished lymphocytes, monocytes and granulocytes. The diagnostic accuracy to discriminate MDS patients from patients without MDS/AML was evaluated by setting different cut-offs based on the percentage of MNDA-dim myeloid cells. Using selected surface antigens, the myeloid subset with MNDA-dim cells was further immunophenotyped to more accurately characterize this cell type. Result: A specific myeloid subset with diminished MNDA expression was found in MDS patients, and this myeloid subset can be characterized as SSC intermediate-to-hi /CD45 dim /CD14 - /CD66abce - . The sensitivity and specificity of detecting MDS using a 5% cut-off based on the percentage of MNDA-dim myeloid cells were 52.63% and 91.38%, respectively. The expression levels of CD13, CD33 and CD133 on CD66abce - /MNDA dim myeloid cells were significantly higher in MDS patients when compared to patients with disease-free bone marrow (p < 0.05). Conclusion: The diminished expression of MNDA in myeloid subset measured by multiparametric flow cytometry can improve the current diagnosis of MDS. CD66abce have the potential to be used as an independent marker to detect MDS.