ANALYSIS OF
REPERTOIRE AND CLONAL EXPANSION OF T CELLS IN THE BLOOD OF CHILDREN WITH ACUTE
B-LYMPHOBLASTIC LEUKEMIA
Zhang R1, Li ZG1, Wu
MY1, Zhu P2，Hu
YM1
1 Peking
Children’s Hospital, Beijing, China
2 The First Hospital of Peking University,
Beijing, China
Objective: T cells may play an important role in pathogenesis of
acute B lymphoblastic leukemia (B-ALL) in children. Understanding the
mechanisms involved in the immune response against tumor cells is likely to
improve leukemia immunotherapy.
Methods: T cell receptor beta chain variable gene (TCR BV) usage
and complementary determining region 3 (CDR3) size distribution were
analyzed to assess the T-cell repertoire of 15 newly diagnosed patients
with B-ALL and in 10 age-matched healthy control donors. 5 of 15 patients
were determined again after remission. A method combined RT-PCR with
denatured polyacrylamide sequencing gel electrophoresis, which is called
TCR CDR3 spectratyping was used.
Results:
Our data indicate that the T cell
repertiore in B-ALL children is highly diverse in terms of Vβgene-segment subfamily use. The analysis disclosed in
14/15 B-ALL patients a markedly abnormal pattern, with many clonal bands in
1 to 9 subfamilies. While only 4 of 10 blood samples showed 1 to 2 slightly
abnormal bands in a control group. Though we didn’t find the commonly used
TCR BV families in all 14 patients, TCR BV14, 20, 8, 13.1 and 13.2 were
clonally expressed in 8, 6, 5, 5 and 4 of 19 patients. After remission TCR
BV CDR3 repertoire of all 5 patients detected showed normal Gaussian
distribution without clonal expansions.
Conclusion: T cells in the blood of B-ALL childern show impressive
abnormalities with many oligoclonal T cell populations and a very
restricted and skewed TCR BV repertoire. The clonal T cell expansions may
derive from tumor-associated antigen stimulation.