title: 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.
abstract: 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.
authors.affiliation: Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Children's Hospital, Erasmus University Medical Center, Dr Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands.
authors.forename: Amy
authors.initials: A
authors.lastname: Holleman
authors.forename: Monique L
authors.initials: ML
authors.lastname: den Boer
authors.forename: Meyling H
authors.initials: MH
authors.lastname: Cheok
authors.forename: Karin M
authors.initials: KM
authors.lastname: Kazemier
authors.forename: Deqing
authors.initials: D
authors.lastname: Pei
authors.forename: James R
authors.initials: JR
authors.lastname: Downing
authors.forename: Gritta E
authors.initials: GE
authors.lastname: Janka-Schaub
authors.forename: Ulrich
authors.initials: U
authors.lastname: Göbel
authors.forename: Ulrike B
authors.initials: UB
authors.lastname: Graubner
authors.forename: Ching-Hon
authors.initials: CH
authors.lastname: Pui
authors.forename: William E
authors.initials: WE
authors.lastname: Evans
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols; D001483:Base Sequence; D002648:Child; D015331:Cohort Studies; D004273:DNA, Neoplasm / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000145:classification / Q000188:drug therapy* / Q000235:genetics*; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D004273:DNA, Neoplasm