Late recurrence of childhood T-cell acute lymphoblastic leukemia frequently represents a second leukemia rather than a relapse: first evidence for genetic predisposition

Tomasz Szczepanski, Vincent H J van der Velden, Esmé Waanders, Roland P Kuiper, Pieter Van Vlierberghe, Bernd Gruhn, Cornelia Eckert, Renate Panzer-Grümayer, Giuseppe Basso, Hélène Cavé, Udo Zur Stadt, Dario Campana, André Schrauder, Rosemary Sutton, Elisabeth van Wering, Jules P P Meijerink, Jacques J M van Dongen

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Samenvatting

PURPOSE: 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.

PATIENTS AND METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

Originele taal-2Engels
Pagina's (van-tot)1643-9
Aantal pagina's7
TijdschriftJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume29
Nummer van het tijdschrift12
DOI's
StatusGepubliceerd - 20 apr. 2011
Extern gepubliceerdJa

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