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

Objective. Analysis of the alpha beta T-cell receptor (TCR) repertoire in patients with myelodysplastic syndrome (MDS) using the technique of TCR beta-chain spectratyping has provided valuable insight into the pathophysiology of cytopenias in a subset of patients with this heterogeneous disorder. TCR beta-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 beta 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 alpha beta TCR repertoires in 50 MDS patients and 23 age-matched healthy controls. Results. Cluster analysis identified as subset of 11 MDS patients with profoundly abnormal alpha beta 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 alpha beta TCR repertoires between individuals and have shown that abnormal alpha beta TCR repertoire is a feature of a subset of patients with advanced MDS. (C) 2010 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.