Originally published as JCO Early Release 10.1200/JCO.2007.11.5253 on July 23 2007

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Low ERG and BAALC Expression Identifies a New Subgroup of Adult Acute T-Lymphoblastic Leukemia With a Highly Favorable Outcome

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

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

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

Purpose: Expression of the genes ERG (v-ets erythroblastosis virus E26 oncogene homolog) and BAALC (brain and acute leukemia, cytoplasmic) shows similarity during hematopoietic maturation and predicts outcome in acute myeloid leukemia. We hypothesized that like ERG, BAALC expression might be of prognostic significance in acute T-lymphoblastic leukemia (T-ALL) and that ERG and BAALC expression together would better identify the patient's risk profile.

Patients and Methods: ERG and BAALC mRNA expression were determined by real-time reverse transcriptase polymerase chain reaction in 153 adults with T-ALL. Patients were designated low or high ERG expressers and low or high BAALC expressers.

Results: High BAALC expression correlated with a higher frequency of early T-ALL (P < .0001), CD34 positivity (P < .0001), coexpression of myeloid markers (P = .0001), and high ERG expression (P = .03). High BAALC compared with low BAALC patients had an inferior relapse-free survival (RFS; P = .0008) and overall survival (OS; P = .0001). In contrast, patients with low expression of both ERG and BAALC (representing 41% of all T-ALL patients) had the most favorable outcome (P < .0001; 4-year RFS: low ERG/low BAALC 81%; P < .0001; 4-year OS: low ERG/low BAALC 69%). On multivariable analysis, low ERG/low BAALC expression was of independent favorable prognostic significance (RFS, P = .001; OS, P = .003).

Conclusion: Low expression of both ERG and BAALC identifies T-ALL patients with a distinctly favorable long-term outcome.

published online ahead of print at www.jco.org on July 23, 2007.

Supported in part by grants from the Deutsche Krebshilfe (Max Eder Nachwuchsförderung) and Deutsche Forschungsgesellschaft (DFG BA 3363/1-1; C.D. Baldus); and the Leukemia Clinical Research Foundation (C.D. Bloomfield).

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