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 Blood, 15 September 2006, Vol. 108, No. 6, pp. 1984-1990.
Prepublished online as a Blood First Edition Paper on May 18, 2006; DOI 10.1182/blood-2006-04-015990.

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NEOPLASIA

Expression of the outcome predictor in acute leukemia 1 (OPAL1) gene is not an independent prognostic factor in patients treated according to COALL or St Jude protocols

Amy Holleman, Monique L. den Boer, Meyling H. Cheok, Karin M. Kazemier, Deqing Pei, James R. Downing, Gritta E. Janka-Schaub, Ulrich Göbel, Ulrike B. Graubner, Ching-Hon Pui, William E. Evans, and Rob Pieters

From the Department of Pediatric Oncology/Hematology, Erasmus MC–Sophia Children's Hospital, Erasmus University Medical Center, Rotterdam, The Netherlands; the Departments of Pharmaceutical Sciences, Biostatistics, and Pathology, Hematology/Oncology, St Jude Children's Research Hospital, Memphis, TN; Department of Hematology/Oncology, University Children's Hospital, Hamburg, Germany; Department of Pediatric Hematology and Oncology, University Medical Center, Heinrich-Heine-University, Düsseldorf, Germany; Department of Pediatric Oncology, Dr von Haunersches Children's Hospital, University of Munich, Germany; and the Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia (COALL) study group.

New prognostic factors may result in better risk classification and improved treatment of children with acute lymphoblastic leukemia (ALL). Recently, high expression of a gene named OPAL1 (outcome predictor in acute leukemia) was reported to be associated with favorable prognosis in ALL. Therefore, we investigated whether OPAL1 expression was of prognostic importance in 2 independent cohorts of children with ALL treated on Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia (COALL)–92/97 (n = 180) and St Jude Total 13 protocols (n = 257). We observed a consistently higher (2.8-fold) expression of OPAL1 in TEL-AML1–positive ALL compared with TEL-AML1–negative ALL in both cohorts, but higher OPAL1 expression was not consistently associated with other favorable prognostic indicators such as age and white blood cell count, or ALL genetic subtype. Lower OPAL1 expression was also not associated with increased in vitro drug resistance. Multivariate analyses including known risk factors showed that OPAL1 expression was not independently related to prognosis in either the COALL or St Jude cohorts. In conclusion, OPAL1 expression may not be an independent prognostic feature in childhood ALL, and its previously reported prognostic impact appears to be treatment dependent.


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