Diagnosis of erythroid dysplasia by flow cytometry: a review

ABSTRACT

Introduction

The diagnosis of myelodysplastic syndrome (MDS) is complex. Flow cytometric analysis of the myelomonocytic compartment can be helpful, but it is highly subjective and reproducibility by non-specialized groups is unclear. Analysis of the erythroid lineage by flow cytometry is emerging as potentially more reproducible and easier to conduct, while keeping a high diagnostic performance.

Areas covered

We review the evidence in this area, including 1) the use of well-established markers – CD71 and CD36 – and other less well-established markers and parameters; 2) the use of flow cytometric scores for the erythroid lineage; and 3) additional aspects, including the emergence of computational tools and the roles of flow cytometry beyond diagnosis. Finally, we discuss the limitations with the current evidence, including 1) the impact of the sample processing protocol and reagents on the results, 2) the lack of a standard gating strategy, and 3) conceptualization and design issues in the available publications.

Expert opinion

We end by offering our recommendations for the current use – and our personal take on the value – of the analysis of erythroid lineage by flow cytometry.

GRAPHICAL ABSTRACT

KEYWORDS:

• CD105
• CD117
• CD36
• CD71
• erythroid
• flow cytometry
• myelodysplastic syndrome
• side scatter

Article highlights

• The diagnosis of myelodysplastic syndrome (MDS) is complex. Flow cytometric analysis of the myelomonocytic compartment can be helpful, but it is highly subjective. Analysis of the erythroid lineage by flow cytometry is emerging as potentially more reproducible and easier to conduct.

• There is robust evidence indicating dimmer expression (and a consequent higher coefficient of variation) of CD71 and CD36 in patients with MDS compared to that of individuals without MDS.

• There is interesting but still preliminary evidence suggesting that the side light scatter of the erythroid lineage is larger in patients with MDS compared to that of individuals without MDS.

• Evidence with other markers (e.g. CD105, CD117) and other parameters (e.g. percentage of erythroid lineage over total cells) has shown less consistent results. Two scores including only erythroid parameters have been published.

• Computational tools for the analysis of the erythroid lineage in the diagnostic laboratory are rapidly becoming available and are likely to be more reproducible than manual analysis.

• A number of limitations or challenges to the analysis of the erythroid lineage are likely to underlie part of the inconsistencies between published reports and could block or slow down satisfactory implementation of this analysis into the clinical laboratory. These limitations include, most importantly, (1) the heterogeneity of sample processing protocols – particularly, lysing techniques and reagents – and gating strategies as well as (2) the heterogeneity in patients and controls and the suboptimal gold standard used in most studies.

Declaration of interest

M Sorigue has received travel expenses and honoraria from Beckman Coulter. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.