Abnormalities of the αβ T-cell receptor repertoire in advanced myelodysplastic syndrome
Received 20 August 2009; received in revised form 22 November 2009; accepted 15 December 2009. published online 25 December 2009.
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.
aProgram in Immunology, Fred Hutchinson Cancer Research Center, Seattle, Wash., USA
bProgram in Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, Wash., USA
cProgram in Transplantation Biology, Fred Hutchinson Cancer Research Center, Seattle, Wash., USA
dDepartment of Medicine, University of Washington, Seattle, Wash., USA
Offprint requests to: Edus H. Warren, M.D., Ph.D., Program in Immunology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, D3-100, P.O. 19024, Seattle, WA 98109-1024
∗ Drs. Campregher and Srivastava contributed equally to this work.
ABSTRACT