Biologic pathways associated with relapse in childhood acute lymphoblastic leukemia: A Children's Oncology Group study

Deepa Bhojwani, Huining Kang, Naomi P. Moskowitz, Dong Joon Min, Hokyung Lee, Jeffrey W. Potter, George Davidson, Cheryl L. Willman, Michael J. Borowitz, Ilana Belitskaya-Levy, Stephen P. Hunger, Elizabeth A. Raetz, William L. Carroll

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)711-717
Number of pages7
JournalBlood
Volume108
Issue number2
DOIs
StatePublished - Jul 15 2006
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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