A New Recurrent 9q34 Duplication in Pediatric T-Cell Acute Lymphoblastic Leukemia.

Over the last decade, genetic characterization of pediatric T cell acute lymphoblastic leukemia (T-ALL) has led to the identification of a variety of chromosomal abnormalities, including translocations, deletions and amplifications. In this study, we used array-comparative genome hybridization (array-CGH) to identify a novel recurrent 9q34 amplification in 33 percent (12/36) of pediatric T-ALL samples, which is therefore one of the most frequent cytogenetic abnormalities observed in T-ALL thus far. The exact size of the amplified region differed slightly among patients, but the critical region involved VAV2, TRAF2 and NOTCH1. FISH analysis revealed that this 9q34 amplification was the result of a 9q34 duplication on one chromosome and could be identified in 17 to 39 percent of the leukemic cells at diagnosis. Although the presence of this leukemic subclone did not predict for poor clinical outcome in our small patient cohort, leukemic cells carrying this duplication were still present at times of relapse, indicating that these cells effectively survived intensive chemotherapeutic treatment. Episomal NUP214-ABL1 amplification and activating mutations in NOTCH1, two other recently identified 9q34 abnormalities in T-ALL, were also detected in our pediatric patient cohort. We showed that both genetic abnormalities are independent from this newly identified 9q34 duplication.