Abnormalities of the αβ T-cell receptor repertoire in advanced myelodysplastic syndrome

Objective

Analysis of the αβ T-cell receptor (TCR) repertoire in patients with myelodysplastic syndrome (MDS) using the technique of TCR β-chain spectratyping has provided valuable insight into the pathophysiology of cytopenias in a subset of patients with this heterogeneous disorder. TCR β-chain spectratypes are complex data sets, however, and statistical tools for their comprehensive analysis are limited. The objective of the present work was to develop a method to enable quantitative evaluation and global comparison of spectratype data from different individuals and to study the prevalence of TCR β repertoire abnormalities in MDS patients.

Materials and Methods

We developed a robust statistical method based on k-means clustering analysis, and applied this method to analysis of the αβ TCR repertoires in 50 MDS patients and 23 age-matched healthy controls.

Results

Cluster analysis identified a subset of 11 MDS patients with profoundly abnormal αβ TCR repertoires. This group of patients was characterized by advanced disease by International Prognostic Scoring System and World Health Organization criteria, increased expression of the Wilms' tumor-1 oncogene, increased bone marrow myeloblast count, and older age.

Conclusions

We have developed a robust analytic algorithm that enables the comparison of αβ TCR repertoires between individuals and have shown that abnormal αβ TCR repertoire is a feature of a subset of patients with advanced MDS.