***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 result ing 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+ ( NOTCH1 and /or FBXW7 mutated ) . Although clinical presentations were not significantly associated with NOTCH status , NOTCH+ patients showed a better early response to chemotherapy as compared with NOTCH− patients , according to the rate of poor pre-phase ‘ responders ’ ( 25 % versus 44 % ; P=0.02 ) and the incidence of high minimal residual disease ( MRD ) levels ( 11 % ( 7/62 ) versus 32 % ( 10/31 ) ; P=0.01 ) at completion of induction . However , the outcome of NOTCH+ patients was similar to that of NOTCH− patients , with a 5-year event-free survival ( EFS ) of 73 % and 70 % ( P=0.82 ) , and 5-year overall survival of 82 % and 79 % ( P=0.62 ) , respectively . In patients with high MRD levels  , the 5-year EFS rate was 0 % ( NOTCH+ ) versus 42 % ( NOTCH− ) , whereas in those with low MRD levels , the outcome was similar : 76 % ( NOTCH+ ) versus 78 % ( NOTCH− ) . The incidence of isolated central nervous system ( CNS ) relapses was relatively high in NOTCH1 + patients ( 8.3 % ) , which could be related to a higher propensity of NOTCH+ leukemic blasts to target the CNS PURPOSE Pediatric T-cell lymphoblastic lymphomas ( T-LBL ) are commonly treated on T-cell acute lymphoblastic leukemia ( T-ALL ) -derived protocol s. Therapeutic stratification based on response to the prephase treatment and on minimal residual disease assessment is well established in T-ALL but is not easy to extrapolate to T-LBL . The identification of molecular prognostic markers at diagnosis in T-LBL could provide an alternative for early therapeutic stratification . Our study determines the frequency and prognostic value of NOTCH1/FBXW7 mutations ( N/F(mut ) ) , FLASH deletion at chromosome 6q , and TCR rearrangements in a prospect i ve cohort of pediatric T-LBL . PATIENTS AND METHODS Pathologic sample s were obtained at diagnosis for 54 patients treated according to the EuroLB02 protocol in France . N/F(mut ) were identified by direct sequencing and allelic dosage was used to detect FLASH and TCRγ deletions , which were interpreted in conjunction with TCRγ , TCRβ , and TCRδ rearrangements . RESULTS N/F(mut ) were found in 55 % of T-LBL patients , in whom they were associated with improved event-free survival ( P < .01 ) and overall survival ( P < .01 ) . FLASH monoallelic deletions were observed in 18 % of patients ; they were predominantly N/F wild-type ( six of nine ) and tended to be of inferior prognosis ( P = .09 ) . Absence of biallelic TCRγ deletion ( ABD ) was seen in 7 % , all of which were N/F(mut ) and identified a poor prognosis group ( P = .02 ) . On multivariate analysis of N/F(mut ) , TCRγ ABD , and FLASH deletion , only N/F(mut ) was an independent factor for good prognosis . CONCLUSION Mutational status of NOTCH1/FBXW7 represents a promising marker for early therapeutic stratification in pediatric T-LBL PURPOSE The Group for Research in Adult Acute Lymphoblastic Leukemia ( GRAALL ) recently reported a significantly better outcome in T-cell acute lymphoblastic leukemia ( T-ALL ) harboring NOTCH1 and /or FBXW7 ( N/F ) mutations compared with unmutated T-ALL . Despite this , one third of patients with N/F-mutated T-ALL experienced relapse . PATIENTS AND METHODS In a series of 212 adult T-ALLs included in the multicenter r and omized GRAALL-2003 and -2005 trials , we search ed for additional N/K-RAS mutations and PTEN defects ( mutations and gene deletion ) . RESULTS N/F mutations were identified in 143 ( 67 % ) of 212 patients , and lack of N/F mutation was confirmed to be associated with a poor prognosis . K-RAS , N-RAS , and PTEN mutations/deletions were identified in three ( 1.6 % ) of 191 , 17 ( 8.9 % ) of 191 , and 21 ( 12 % ) of 175 patients , respectively . The favorable prognostic significance of N/F mutations was restricted to patients without RAS/PTEN abnormalities . These observations led us to propose a new T-ALL oncogenetic classifier defining low-risk patients as those with N/F mutation but no RAS/PTEN mutation ( 97 of 189 patients ; 51 % ) and all other patients ( 49 % ; including 13 % with N/F and RAS/PTEN mutations ) as high-risk patients . In multivariable analysis , this oncogenetic classifier remained the only significant prognostic covariate ( event-free survival : hazard ratio [ HR ] , 3.2 ; 95 % CI , 1.9 to 5.15 ; P < .001 ; and overall survival : HR , 3.2 ; 95 % CI , 1.9 to 5.6 ; P < .001 ) . CONCLUSION These data demonstrate that the presence of N/F mutations in the absence of RAS or PTEN abnormalities predicts good outcome in almost 50 % of adult T-ALL . Conversely , the absence of N/F or presence of RAS/PTEN alterations identifies the remaining cohort of patients with poor prognosis Activating mutations of the transmembrane receptor NOTCH1 are common in precursor T-cell lymphoblastic leukemia ( T-ALL ) . We systematic ally analyzed the impact of activating NOTCH1 mutations on early treatment response and long-term outcome in 157 patients with T-ALL of the pediatric ALL-Berlin-Frankfurt-Munster ( BFM ) 2000 study . We confirm previous results that NOTCH1 mutations occur in more than 50 % of T-ALL in children . In 82 patients ( 82/157 ; 52.2 % ) , activating NOTCH1 mutations were identified either in the heterodimerization ( 55/82 ; 67.1 % ) , in the PEST ( 13/82 ; 15.9 % ) , or in both domains ( 14/82 ; 17.0 % ) . The presence of NOTCH1 mutations was significantly correlated with a good prednisone response and favorable minimal residual disease ( MRD ) kinetics , which was independent from sex , age , white blood cell count , and T-cell immunophenotype at the time of diagnosis . Furthermore , activating NOTCH1 mutations specified a large subgroup of patients with an excellent prognosis . These findings indicate that in the context of the ALL-BFM 2000 treatment strategy , NOTCH1 mutations predict a more rapid early treatment response and a favorable long-term outcome in children with T-ALL Adult T-cell acute lymphoblastic leukemia ( T-ALL ) is an aggressive hematologic tumor associated with poor outcome . In this study , we analyzed the prognostic relevance of genetic alterations , immunophenotypic markers , and microarray gene expression signatures  in a panel of 53 adult T-ALL patients treated in the Eastern Cooperative Oncology Group E2993 clinical trial . An early immature gene expression signature , the absence of bi-allelic TCRG deletion , CD13 surface expression , heterozygous deletions of the short arm of chromosome 17 , and mutations in IDH1/IDH2 and DNMT3A genes are associated with poor prognosis in this series . In contrast , expression of CD8 or CD62L , homozygous deletion of CDKN2A/CDKN2B , NOTCH1 and /or FBXW7 mutations , and mutations or deletions in the BCL11B tumor suppressor gene were associated with improved overall survival . Importantly , the prognostic relevance of CD13 expression and homozygous CDKN2A/CDKN2B deletions was restricted to cortical and mature T-ALLs . Conversely , mutations in IDH1/IDH2 and DNMT3A were specifically associated with poor outcome in early immature adult T-ALLs . This trial was registered at www . clinical trials.gov as # NCT00002514 
    Output:
    
We conclude that the presence of NOTCH1/FBXW7 mutations is an independent prognostic factor for 5-year EFS and 5-year OS