In a series of 153 children with T-cell malignancies enrolled in 2 consecutive European Organization for Research and Treatment of Cancer (EORTC) trials, we assessed the HOX11L2 expression and/or the presence of a t(5;14)(q35;q32). Additionally, in 138 of these patients, HOX11 expression and SIL-TAL rearrangement were also assessed. These alterations were mutually exclusive, and their frequency was 23% (n ‫؍‬ 35), 7% (n ‫؍‬ 10), and 12% (n ‫؍‬ 17), respectively. HOX11L2/ t(5;14) positivity was more frequent in acute lymphoblastic leukemia (ALL) with cortical T immunophenotype and in children aged between 6 and 9 years. In contrast with previously reported data, patients positive and negative for HOX11L2/t(5;14) were comparable with regard to clinical outcome as well as to the response to a 7-day prephase treatment or to residual disease at completion of induction therapy.

Risk-adjusted treatment stratification in T-cell acute lymphoblastic leukemias (T-ALLs) is currently based only on early response to chemotherapy. We investigated the prognostic implication of hyperactivation of NOTCH pathway resulting from mutations of NOTCH1 or FBXW7 in children with T-ALL enrolled in EORTC-CLG trials. Overall, 80 out of 134 (60%) patients were NOTCH þ (NOTCH1 and/or FBXW7 mutated). Although clinical presentations were not significantly associated with NOTCH status, NOTCH þ patients showed a better early response to chemotherapy as compared with NOTCHÀ patients, according to the rate of poor pre-phase 'responders' (25% versus 44%; P ¼ 0.02) and the incidence of high minimal residual disease (MRD) levels (11% (7/62) versus 32% (10/31); P ¼ 0.01) at completion of induction. However, the outcome of NOTCH þ patients was similar to that of NOTCHÀ patients, with a 5-year event-free survival (EFS) of 73% and 70% (P ¼ 0.82), and 5-year overall survival of 82% and 79% (P ¼ 0.62), respectively. In patients with high MRD levels, the 5-year EFS rate was 0% (NOTCH þ ) versus 42% (NOTCHÀ), whereas in those with low MRD levels, the outcome was similar: 76% (NOTCH þ ) versus 78% (NOTCHÀ). The incidence of isolated central nervous system (CNS) relapses was relatively high in NOTCH1 þ patients (8.3%), which could be related to a higher propensity of NOTCH þ leukemic blasts to target the CNS.

The presence of ETV6 deletions was investigated in 215 chilof t(5;12) 10 and was subsequently found to be fused to a dren with acute lymphoblastic leukemia (ALL) using the loss number of different partners as a result of various leukemiaof heterozygosity (LOH) approach. We used four intragenic or associated translocations. [11][12][13] In pediatric B lineage ALL, juxtagenic microsatellite markers to detect allelic deletions. In t(12;21)(p13;q22), which leads to the formation of a ETV6- region of deletion that did not include ETV6 was found near

Summary. Strategies currently used for residual disease detection in acute lymphoblastic leukaemia (ALL) rely on polymerase chain reaction (PCR) detection of immunoglobulin and T-cell receptor rearrangements. The TEL± AML1 fusion transcript, which is associated with t(12;21) (p13;q22), is found in 25% of childhood B-cell precursor ALL, and represents an interesting alternative target. We compared two methods for quantitating TEL±AML1 fusion transcripts: competitive PCR and real-time PCR. These techniques showed similar sensitivity (5 Â 10 25) and reproducibility. Giving highly correlated results, both techniques can be conveniently used for TEL±AML1 transcript quantification. The constancy of TEL±AML1 expression was evaluated by measuring TEL±AML1 transcripts at different steps of the cell cycle, and in 21 cases of ALL at diagnosis. No major variation in TEL±AML1 expression was observed during the cell cycle or in 20/21 of the ALL patients. Residual disease was then determined after completion of induction therapy in 20 patients with a TEL±AML1-positive ALL. Seven patients out of 20 (35%) were still positive, including two patients with high level of residual blasts (close to or beyond 10 22 ). When comparison was possible, results obtained using TEL±AML1 quantification were in accordance with those obtained using T-cell receptor rearrangements analysis.