Comparative analysis of T-cell receptor gene rearrangements at diagnosis and relapse of T-cell acute lymphoblastic leukemia (T-ALL) shows high stability of clonal markers for monitoring of minimal residual disease and reveals the occurrence of second T-AL

Abstract:

:A total of 28 children and nine adults with relapsed T-ALL were analyzed for the configuration of their T-cell receptor (TCR) and TAL1 genes at diagnosis and relapse to evaluate their stability throughout the disease course. A total of 150 clonal TCR and TAL1 gene rearrangements were identified in the 37 patients at diagnosis. In 65% of cases all rearrangements and in 27% of cases most rearrangements found at diagnosis were preserved at relapse. Two children with unusually late T-ALL recurrences displayed completely different TCR gene rearrangement sequences between diagnosis and relapse. This indicates that a proportion of very late T-ALL recurrences might represent second T-ALL. Specifically, 88% of clonal rearrangements identified at diagnosis in truly relapsed T-ALL were preserved at relapse. This is significantly higher as compared to previously studied precursor-B-ALL ( approximately 70%). Thus, from biological point of view, immunogenotype of T-ALL is more stable as compared with precursor-B-ALL. The overall stability of TCR gene rearrangements was higher in adult T-ALL (97%) than in childhood T-ALL (86%). Based on the stability of TCR gene rearrangements, we propose a strategy for PCR target selection (TCRD+TAL1 --> TCRB --> TCRG), which probably allows reliable minimal residual disease detection in all T-ALL patients.

journal_name

Leukemia

journal_title

Leukemia

authors

Szczepański T,van der Velden VH,Raff T,Jacobs DC,van Wering ER,Brüggemann M,Kneba M,van Dongen JJ

doi

10.1038/sj.leu.2403081

subject

Has Abstract

pub_date

2003-11-01 00:00:00

pages

2149-56

issue

11

eissn

0887-6924

issn

1476-5551

pii

2403081

journal_volume

17

pub_type

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