title: Genes contributing to minimal residual disease in childhood acute lymphoblastic leukemia: prognostic significance of CASP8AP2.
abstract: In childhood acute lymphoblastic leukemia (ALL), early response to treatment is a powerful prognostic indicator. To identify genes associated with this response, we analyzed gene expression of diagnostic lymphoblasts from 189 children with ALL and compared the findings with minimal residual disease (MRD) levels on days 19 and 46 of remission induction treatment. After excluding genes associated with genetic subgroups, we identified 17 genes that were significantly associated with MRD. The caspase 8-associated protein 2 (CASP8AP2) gene was studied further because of its reported role in apoptosis and glucocorticoid signaling. In a separate cohort of 99 patients not included in the comparison of gene expression profiles and MRD, low levels of CASP8AP2 expression predicted a lower event-free survival (P = .02) and a higher rate of leukemia relapse (P = .01) and were an independent predictor of outcome. High levels of CASP8AP2 expression were associated with a greater propensity of leukemic lymphoblasts to undergo apoptosis. We conclude that measurement of CASP8AP2 expression at diagnosis offers a means to identify patients whose leukemic cells are highly susceptible to chemotherapy. Therefore, this gene is a strong candidate for inclusion in gene expression arrays specifically designed for leukemia diagnosis.
authors.affiliation: Department of Pathology, St Jude Children's Research Hospital, 332 N Lauderdale, Memphis, TN 38105, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Flotho
authors.forename: Elaine
authors.initials: E
authors.lastname: Coustan-Smith
authors.forename: Deqing
authors.initials: D
authors.lastname: Pei
authors.forename: Shotaro
authors.initials: S
authors.lastname: Iwamoto
authors.forename: Guangchun
authors.initials: G
authors.lastname: Song
authors.forename: Cheng
authors.initials: C
authors.lastname: Cheng
authors.forename: Ching-Hon
authors.initials: CH
authors.lastname: Pui
authors.forename: James R
authors.initials: JR
authors.lastname: Downing
authors.forename: Dario
authors.initials: D
authors.lastname: Campana
mesh_terms: D000293:Adolescent; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D008297:Male; D018365:Neoplasm, Residual / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000235:genetics*; D011237:Predictive Value of Tests; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D051017:Apoptosis Regulatory Proteins; C485604:CASP8AP2 protein, human; D002135:Calcium-Binding Proteins