Abnormalities of the alphabeta T-cell receptor repertoire in advanced myelodysplastic syndrome.
OBJECTIVE
Analysis of the alphabeta 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.


METHODS
We developed a robust statistical method based on k-means clustering analysis, and applied this method to analysis of the alphabeta 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 alphabeta 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 alphabeta TCR repertoires between individuals and have shown that abnormal alphabeta TCR repertoire is a feature of a subset of patients with advanced MDS.
Campregher
Paulo V
PV
Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, Wash. 98109-1024, USA.
Srivastava
Santosh K
SK
Deeg
H Joachim
HJ
Robins
Harlan S
HS
Warren
Edus H
EH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D016000:Cluster Analysis; D022801:Complementarity Determining Regions / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
D022801:Complementarity Determining Regions; D016693:Receptors, Antigen, T-Cell, alpha-beta