title: Biologic pathways associated with relapse in childhood acute lymphoblastic leukemia: a Children's Oncology Group study.
abstract: Outcome for children with childhood acute lymphoblastic leukemia (ALL) who relapse is poor. To gain insight into the mechanisms of relapse, we analyzed gene-expression profiles in 35 matched diagnosis/relapse pairs as well as 60 uniformly treated children at relapse using the Affymetrix platform. Matched-pair analyses revealed significant differences in the expression of genes involved in cell-cycle regulation, DNA repair, and apoptosis between diagnostic and early-relapse samples. Many of these pathways have been implicated in tumorigenesis previously and are attractive targets for intervention strategies. In contrast, no common pattern of changes was observed among late-relapse pairs. Early-relapse samples were more likely to be similar to their respective diagnostic sample while we noted greater divergence in gene-expression patterns among late-relapse pairs. Comparison of expression profiles of early- versus late-relapse samples indicated that early-relapse clones were characterized by overexpression of biologic pathways associated with cell-cycle regulation. These results suggest that early-relapse results from the emergence of a related clone, characterized by the up-regulation of genes mediating cell proliferation. In contrast, late relapse appears to be mediated by diverse pathways.
authors.affiliation: New York University (NYU) Cancer Institute and Division of Pediatric Hematology/Oncology, NY 10016, USA.
authors.forename: Deepa
authors.initials: D
authors.lastname: Bhojwani
authors.forename: Huining
authors.initials: H
authors.lastname: Kang
authors.forename: Naomi P
authors.initials: NP
authors.lastname: Moskowitz
authors.forename: Dong-Joon
authors.initials: DJ
authors.lastname: Min
authors.forename: Hokyung
authors.initials: H
authors.lastname: Lee
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Potter
authors.forename: George
authors.initials: G
authors.lastname: Davidson
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Willman
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Borowitz
authors.forename: Ilana
authors.initials: I
authors.lastname: Belitskaya-Levy
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Hunger
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Raetz
authors.forename: William L
authors.initials: WL
authors.lastname: Carroll
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D049109:Cell Proliferation; D002648:Child; D002999:Clone Cells / Q000473:pathology; D004260:DNA Repair / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D016555:Matched-Pair Analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology*; D012008:Recurrence; D013997:Time Factors