Late Recurrence of Childhood T-Cell Acute Lymphoblastic Leukemia Frequently Represents a Second Leukemia Rather Than a Relapse: First Evidence for Genetic Predisposition
- 20 April 2011
- journal article
- research article
- Published by American Society of Clinical Oncology (ASCO) in Journal of Clinical Oncology
- Vol. 29 (12), 1643-1649
- https://doi.org/10.1200/jco.2010.30.2877
Abstract
Relapse of childhood T-cell acute lymphoblastic leukemia (T-ALL) often occurs during treatment, but in some cases, leukemia re-emerges off therapy. On the basis of previous analyses of T-cell receptor (TCR) gene rearrangement patterns, we hypothesized that some late recurrences of T-ALL might in fact represent second leukemias. In 22 patients with T-ALL who had late relapses (at least 2.5 years from diagnosis), we studied TCR gene rearrangement status at first and second presentation, NOTCH1 gene mutations, and the presence of the SIL-TAL1 gene fusion. We performed genome-wide copy number and homozygosity analysis by using oligonucleotide- and single nucleotide polymorphism (SNP) –based arrays. We found evidence of a common clonal origin between diagnosis and relapse in 14 patients (64%). This was based on concordant TCR gene rearrangements (12 patients) or concordant genetic aberrations, as revealed by genome-wide copy number analysis (two patients). In the remaining eight patients (36%), TCR gene rearrangement sequences had completely changed between diagnosis and relapse, and gene copy number analysis showed markedly different patterns of genomic aberrations, suggesting a second T-ALL rather than a resurgence of the original clone. Moreover, NOTCH1 mutation patterns were different at diagnosis and relapse in five of these eight patients. In one patient with a second T-ALL, SNP analysis revealed a germline del(11)(p12;p13), a known recurrent aberration in T-ALL. More than one third of late T-ALL recurrences are, in fact, second leukemias. Germline genetic abnormalities might contribute to the susceptibility of some patients to develop T-ALL.Keywords
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