Immunophenotypic analysis of erythroid dysplasia in myelodysplastic syndromes. A report from the IMDSFlow working group
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Database-guided Flow-cytometry for Evaluation of Bone Marrow Myeloid Cell Maturation
Published on: November 3, 2018
Theresia M Westers1, Eline M P Cremers2, Uta Oelschlaegel3
1Department of Hematology, VU University Medical Center, Cancer Center Amsterdam, The Netherlands tm.westers@VUmc.nl.
Insights
Flow cytometry analysis of nucleated erythroid cells can help diagnose myelodysplastic syndromes (MDS). A specific combination of markers (CD36, CD71, CD117) accurately distinguishes MDS-related dyserythropoiesis from other cytopenias.
Area of Science:
- Hematology
- Clinical Pathology
- Immunophenotyping
Background:
- Current myelodysplastic syndromes (MDS) diagnosis relies on flow cytometry, primarily examining progenitor and myelomonocytic cells.
- Anemia and dyserythropoiesis are common in MDS, suggesting a need for erythroid cell analysis.
- Existing flow cytometry protocols may not fully capture erythroid-specific changes in MDS.
Purpose of the Study:
- To identify flow cytometry parameters for discriminating MDS-associated dyserythropoiesis from non-clonal cytopenias.
- To validate these parameters in independent patient cohorts.
- To enhance the diagnostic utility of flow cytometry in suspected MDS cases.
Main Methods:
- A multicenter study involving learning and validation cohorts of MDS patients and controls.
- Analysis of flow cytometry features in nucleated erythroid cells, focusing on CD36, CD71, and CD117 expression.
- Multivariate logistic regression to identify discriminatory marker combinations.
Main Results:
- A combination of CD36 and CD71 (coefficient of variation), CD71 fluorescence intensity, and CD117+ erythroid progenitors showed high specificity in the learning cohort (90%).
- This marker set achieved 92% specificity in the validation cohort, confirming its diagnostic value.
- The findings suggest improved discrimination between MDS and non-clonal cytopenias.
Conclusions:
- Erythroid cell flow cytometry offers a valuable complement to existing MDS diagnostic tools.
- The identified marker combination enhances the evaluation of cytopenic patients with suspected MDS.
- This approach may improve diagnostic accuracy, especially when integrated with myelomonocytic lineage assessment.
Abstract:
Current recommendations for diagnosing myelodysplastic syndromes endorse flow cytometry as an informative tool. Most flow cytometry protocols focus on the analysis of progenitor cells and the evaluation of the maturing myelomonocytic lineage. However, one of the most frequently observed features of myelodysplastic syndromes is anemia, which may be associated with dyserythropoiesis. Therefore, analysis of changes in flow cytometry features of nucleated erythroid cells may complement current flow cytometry tools. The multicenter study within the IMDSFlow Working Group, reported herein, focused on defining flow cytometry parameters that enable discrimination of dyserythropoiesis associated with myelodysplastic syndromes from non-clonal cytopenias. Data from a learning cohort were compared between myelodysplasia and controls, and results were validated in a separate cohort. The learning cohort comprised 245 myelodysplasia cases, 290 pathological, and 142 normal controls; the validation cohort comprised 129 myelodysplasia cases, 153 pathological, and 49 normal controls. Multivariate logistic regression analysis performed in the learning cohort revealed that analysis of expression of CD36 and CD71 (expressed as coefficient of variation), in combination with CD71 fluorescence intensity and the percentage of CD117+ erythroid progenitors provided the best discrimination between myelodysplastic syndromes and non-clonal cytopenias (specificity 90%; 95% confidence interval: 84-94%). The high specificity of this marker set was confirmed in the validation cohort (92%; 95% confidence interval: 86-97%). This erythroid flow cytometry marker combination may improve the evaluation of cytopenic cases with suspected myelodysplasia, particularly when combined with flow cytometry assessment of the myelomonocytic lineage.
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