• Finding: Late-recurring T-ALL can be a second leukemia.

  • Significance: First evidence suggesting genetic predisposition.

  • Impact: Second T-ALL might respond to first-line therapy.

T-cell acute lymphoblastic leukemia (T-ALL) is a childhood disease that has an approximately 75% rate of 5-year event-free survival. However, relapse often occurs on or just after treatment, and prognosis for these patients is very poor. In a recent article, Szczepański and colleagues examined 22 patients with T-ALL that relapsed more than 2.5 years after diagnosis to determine whether these disease recurrences represented a second, independent disease. The authors found clonal T-cell receptor (TCR) rearrangements in 20 of the 22 patients. In 12 of these 20 patients, identical TCR rearrangements were seen at diagnosis and in the relapsed cancer. Strikingly, however, in the other 8 patients, the clonal TCR rearrangements seen at diagnosis were absent in the second disease. Comparative genomic hybridization array analysis showed that 7 of these 8 patients had completely different patterns of copy number variation between first and second disease. In the other patient, a well-known somatic microdeletion was observed. Finally, the authors were unable to detect any genetic markers of the second disease in samples of the original disease. These data suggest that a significant percentage of late relapsing T-ALL may in fact represent new disease, and it is possible that these patients have a genetic predisposition to T-ALL development.

Szczepański T, van der Velden VH, Waanders E, Kuiper RP, Van Vlierberghe P, Gruhn B, et al. Late recurrence of childhood T-cell acute lymphoblastic leukemia frequently represents a second leukemia rather than a relapse: first evidence for genetic predisposition. J Clin Oncol 2011;29:1643–9.

Note:Research Watch is written by Cancer Discovery Editors. Readers are encouraged to consult the articles referred to in each item for full details on the findings described.