Introduction:
Relapses are still the major cause of poor outcome in therapy of T-lineage acute lymphoblastic
leukemia (T-ALL) in children. Over 30% cases of relapse in T-ALL are accompanied by
changing of the main clones. At the present time the most reliable markers for analysis
of clonal structure of T-ALL are rearrangements of T-cell receptors (TCR) genes: TCR
beta, gamma and delta. The purpose of this study is identification and characterization
a new type of clonal markers based on previously unanalyzed in ALL rearrangements
of TCR alpha locus.
Material and Methods:
Detection of TCR alpha genes rearrangements was based on high-throughput sequencing
of amplicons obtained in series of multiplex PCR with genomic DNA from bone marrow
and primers for all major V- and J-genes combination of TCR alpha locus.
Results:
We analyzed 75 samples of T-ALL in which we identified over 90 clonal rearrangements
of TCR alpha locus. 15 samples contained rearrangements with clonal rate more than
40%, 37 samples contained 1 – 4 rearrangements with lower clonal rate (5 – 35%), 23
samples didn't contain any leukemia specific TCR alpha rearrangements.
Conclusion:
For the first time we evaluated frequency of clonal rearrangements of TCR alpha locus
in pediatric T-ALL. This type of markers is presented in more than half of T-ALL cases
what makes them fully applicable for analysis of clonal structure of T-ALL in both
onset and relapse.
Funding: Russian Science Foundation grant # 17 – 75 – 10113.
