The Wilms tumor 1 (WT1) gene, located on chromosome band 11p13, encodes a transcriptional regulator involved in normal hematopoietic development. The WT1 protein contains an N-terminal domain (exons 1–6) and a C-terminal domain with 4 zinc finger motifs (exons 7–10). The role of WT1 in acute leukemia has been underscored by the finding of WT1 overexpression in most cases of acute myeloid leukemia (AML). 1 WT1 mutations have been identified in B10% of patients with AML and have been found to predict poor outcome. 2–4 WT1 mutations in T-lineage acute lymphoblastic leukemia (T-ALL) were first described more than 10 years ago by King-Underwood and Pritchard-Jones5 in one pediatric case, but were no longer investigated until recently. Our aim was to evaluate the frequency, main associated features and prognostic significance of WT1 mutations in a cohort of children with T-cell malignancies. A total of 157 children, aged between 7 months and 17 years, with newly diagnosed T-ALL (n¼ 143) or T-cell lymphoblastic lymphoma (n¼ 14), were included in this study. Patients were treated according to two consecutive clinical protocols conducted by the CLG-EORTC (Childrens Leukemia Group of the European Organisation for Research and Treatment of Cancer): studies 58881 and 58951. These protocols have been accepted by the EORTC Protocol Review Committee and by the Ethics Committee of each participating center. Informed consent was obtained from the patients or their guardians, in accordance with the declaration of Helsinki. The main characteristics of the T-ALL patients studied are described in Table 1. T-cell lineage assessment and classification were performed according to the European Group for the Immunological Characterization of Leukemias (EGIL) recommendations. 6 Standard karyotype and screening of MLL rearrangements by fluorescent in situ hybridization analysis were performed at the time of diagnosis. The presence of an overexpression of HOX11/TLX1, HOX11L2/TLX3 and HOXA10 genes, as well as that of SIL-TAL, CALMAF10 and NUP214-ABL fusion transcripts was assessed by realtime quantitative reverse transcriptase-PCR as described elsewhere. 7 WT1 expression level was measured by real-time quantitative reverse transcriptase-PCR using the European Leukemia Net Standardized Assay. 1 MYB duplications were detected by gene dosage using real-time quantitative PCR. 8 Mutations of NOTCH1 exons 26, 27, 28 and 34, FBXW7 exons 9 and 10, and WT1 exon 7 and 9 were screened by direct sequencing, as described previously. 3, 9, 10 Statistical analysis of patient characteristics was performed using the Fisher exact test for binary variables and the Mann–Whitney test for continuous variables. Event-free survival and overall survival were