Originally published as JCO Early Release 10.1200/JCO.2006.06.1580 on September 5 2006

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High Expression of the ETS Transcription Factor ERG Predicts Adverse Outcome in Acute T-Lymphoblastic Leukemia in Adults

Claudia D. Baldus, Thomas Burmeister, Peter Martus, Stefan Schwartz, Nicola Gökbuget, Clara D. Bloomfield, Dieter Hoelzer, Eckhard Thiel, Wolf K. Hofmann

From the Department of Hematology, Oncology, and Transfusion Medicine; Department of Biostatistics and Clinical Epidemiology, Charité, Campus Benjamin Franklin Berlin, University Hospital, Berlin; Department of Hematology and Oncology, University of Frankfurt am Main, Frankfurt, Germany; and Ohio State University, Comprehensive Cancer Center, Columbus, OH

Address reprint requests to Claudia D. Baldus, MD, Department of Hematology, Oncology and Transfusion Medicine, Charité, Campus Benjamin Franklin, University Hospital Berlin, Hindenburgdamm 30, 12203 Berlin, Germany; e-mail: claudia.baldus{at}charite.de

PURPOSE: 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.

PATIENTS AND 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.

CONCLUSION: 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.

published online ahead of print at www.jco.org on September 5, 2006.

Supported by grants from the Deutsche Krebshilfe (Max Eder Nachwuchsförderung) and the German Kompetenznetzwerk Akute und chronische Leukämien (C.D. Baldus). The funding sources had no involvement in the study.

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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