title: High expression of the ETS transcription factor ERG predicts adverse outcome in acute T-lymphoblastic leukemia in adults.
abstract: OBJECTIVE
  In adult T-lymphoblastic leukemia (T-ALL) disease-free survival remains limited to 32% to 46%. The adverse prognosis in T-ALL has not been attributed to cytogenetic or molecular aberrations. We have determined the prognostic impact of the oncogenic transcription factor ERG in T-ALL.
  
  
  METHODS
  ERG expression was analyzed by real-time polymerase chain reaction (PCR) in 105 adults with newly diagnosed T-ALL treated on the German ALL protocols. Patients were dichotomized at ERG's median expression into low (n = 52) and high (n = 53) expressers. Homeobox (HOX) 11 and HOX11L2 expression was determined by real-time PCR.
  
  
  RESULTS
  High ERG expressers compared with low ERG expressers had an inferior overall survival (OS, P = .02; 5-year OS: high ERG 26% v low ERG 58%) and relapse-free survival (RFS, P = .003; 5-year RFS: high ERG 34% v low ERG 72%). On multivariable analysis high ERG expression (P = .005), immunophenotypic subgroups (early v mature v thymic T-ALL; overall P = .04), HOX11L2 positivity (P = .055), and absence of HOX11 (P = .017) were independent adverse risk factors predicting RFS. Patients with high ERG expression had a hazard ratio (HR) for relapse of 3.2. Within the good prognostic subgroup of thymic T-ALL (n = 57), high ERG (HR, 4.1; P = .02) and presence of HOX11L2 (HR, 6.6; P = .008) were independent adverse factors for RFS.
  
  
  CONCLUSIONS
  High expression of ERG is an adverse risk factor in adult T-ALL. Within thymic T-ALL, otherwise classified as standard-risk, high ERG expression-identified patients that were four times more likely to fail long-term RFS. The prognostic impact of ERG may assist treatment stratification and suggest the need of alternative regimens.
authors.affiliation: Department of Hematology, Oncology and Transfusion Medicine, Charité, Campus Benjamin Franklin, University Hospital Berlin, Hindenburgdamm 30, 12203 Berlin, Germany. claudia.baldus@charite.de
authors.forename: Claudia D
authors.initials: CD
authors.lastname: Baldus
authors.forename: Thomas
authors.initials: T
authors.lastname: Burmeister
authors.forename: Peter
authors.initials: P
authors.lastname: Martus
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwartz
authors.forename: Nicola
authors.initials: N
authors.lastname: Gökbuget
authors.forename: Clara D
authors.initials: CD
authors.lastname: Bloomfield
authors.forename: Dieter
authors.initials: D
authors.lastname: Hoelzer
authors.forename: Eckhard
authors.initials: E
authors.lastname: Thiel
authors.forename: Wolf K
authors.initials: WK
authors.lastname: Hofmann
mesh_terms: D000293:Adolescent; D000328:Adult; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D018398:Homeodomain Proteins; D006801:Humans; D016130:Immunophenotyping; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015513:Oncogene Proteins; D011237:Predictive Value of Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D015534:Trans-Activators / Q000378:metabolism*; D000071230:Transcriptional Regulator ERG; D016896:Treatment Outcome
chemical_list: D004268:DNA-Binding Proteins; C072312:ERG protein, human; D018398:Homeodomain Proteins; D015513:Oncogene Proteins; C489494:TLX3 protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG