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Supplementary Information accompanies this paper on the Leukemia website (http://www.nature.com/leu) Detection of PICALM-MLLT10 (CALM-AF10) and outcome in children with T-lineage acute lymphoblastic leukemia Leukemia (2013) 27, 2419–2421; doi:10.1038/leu.2013.149 Approximately 10–15% of pediatric patients with acute lympho- blastic leukemia (ALL) have a T-cell phenotype. The prognosis of these patients has improved over the last years, owing to the use of more intensive treatment strategies. 1 Characterization of molecular alterations with prognostic impact in T-ALL may be of great help for an early identification of patients at high risk (HR) of failure in whom more intensive treatments, including allogeneic hematopoietic stem cell transplantation, may be considered. PICALM (clathrin-assembly protein-like lymphoid myeloid leukemia gene)-MLLT10 (formerly CALM-AF10) results from a recurring t(10;11)(p13;q14-21) chromosomal translocation and is the most frequent fusion transcript detected in patients with T-ALL, at an overall rate of 10%, including both adults and children. 2 This translocation fuses PICALM (or CALM) and MLLT10 (also called AF10). The Groupe Franc ¸ais de Cytoge ´ne ´ tique He ´ matologique firstly observed this translocation in a patient with histiocytic lymphoma. 3 The immunophenotypic characterization of the leukemic cell bearing this fusion gene showed that mature PICALM-MLLT10-positive cases expressed CD5, T-cell receptor (TCR) g/d and CD4 or CD8 (or both), whereas immature cases, which are currently defined as early-T, expressed few T-lineage markers other than CD5, TdT, cCD3 and CD7, and were often positive for CD13, CD33 or CD34. 4 The presence of PICALM-MLLT10 has been associated with a poor prognosis and several studies included very few children with T-ALL. 4–7 We analyzed a large cohort of children with T-ALL, enrolled in two subsequent AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) protocols, with the aim of evaluating both incidence and prognostic impact of PICALM-MLLT10. From 1 September 2000 to 31 December 2007, a total of 309 patients with T-lineage ALL (11.8% of the total number of children diagnosed with ALL), aged between 1 and 18 years (infants o1 year of age were eligible for a separate protocol), were treated in Italy on the AIEOP- Berlin-Frankfurt-Munster (BFM) ALL-2000 (n ¼ 258 until 31 July 2006) or the subsequent AIEOP R-2006 (n ¼ 51) studies. Leftover biological material for analysis of molecular alterations was available in 187 children. Follow-up was updated at December 2009 and median follow-up was 4.7 years. Detailed information regarding diagnosis, methods, risk stratification based on minimal residual disease (MRD), treatment protocol and statistical analyses are reported on Supplementary Materials. Characteristics of the 187 evaluable children with T-ALL are listed in Table 1; of them, 14 children (7.5%) were positive for PICALM-MLLT10 and their characteristics are listed in Supplementary Table 1. The PICALM-MLLT10 fusion transcript was detected more frequently in males (12 out of 14). Patient’s median age was 7 years (range 2–13). PICALM-MLLT10-positive cases were more likely to present with HR features, including a white blood cell (WBC) count higher than 100 000/ml(n ¼ 8). 1,8 PICALM-MLLT10 fusion transcript was significantly more frequent in patients with cortical and mature T, than in those with early-T immunophenotype (P ¼ 0.02). Eight patients were ‘poor prednisone (PDN) responders’ (PPR), which, by study design, were assigned to the HR group. Based on MRD levels, in the PICALM-MLLT10-positive group, eight children were presented with an intermediate risk pattern and six children with an HR pattern (including three who also were PPR). Based on the type of steroid given in induction, nine children with PICALM-MLLT10-positive T-ALL were treated with PDN and five children were treated with dexamethasone (DXM). Among the PICALM-MLLT10-negative patients, DXM was given to 53 (30%) out of 173 children treated on both AIEOP- Berlin- Frankfurt-Munster ALL-2000 (n ¼ 38) and AIEOP R-2006 (n ¼ 15) studies, respectively. Details on patients’ outcome are shown in Supplementary Table 2. The relapse rate was similar in both PICALM-MLLT10-positive and negative patients. In the group of PICALM-MLLT10-positive patients, relapse occurred in four patients (21.5%) and involved the central nervous system in three: this proportion appears to be higher than in the PICALM-MLLT10-negative counterpart (5.8%; P ¼ 0.02). There was no statistically significant difference in terms of final outcome between PICALM-MLLT10-positive and -negative patients, the 5-year event-free survival (EFS) being 71.4% (SE 12.1) vs 62.5% (SE 3.8) (P ¼ 0.53), respectively (Figure 1a). Consistently, cumulative incidence (CI) of relapse was very similar, as shown in Figure 1b. Same results were obtained after adjusting for risk group in a Cox model (data not shown). When the analysis was restricted to the subgroup of patients with cortical or mature immunophenotype, which included the majority of PICALM-MLLT10-positive patients (n ¼ 12), there was no statistically significant difference between PICALM-MLLT10- Accepted article preview 14 May 2013; advance online publication, 18 June 2013 Letters to the Editor 2419 & 2013 Macmillan Publishers Limited Leukemia (2013) 2376 – 2424