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 journalArticle

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

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Oncology
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Gene expression
Genes
Cells
Recurrence
Cell proliferation
Repair
Apoptosis
DNA
Cell Cycle
Clone Cells
Gene Expression
Matched-Pair Analysis
Transcriptome
DNA Repair
Carcinogenesis
Up-Regulation
Cell Proliferation

ASJC Scopus subject areas

  • Hematology

Cite this

Bhojwani, D., Kang, H., Moskowitz, N. P., Min, D. J., Lee, H., Potter, J. W., ... Carroll, W. L. (2006). Biologic pathways associated with relapse in childhood acute lymphoblastic leukemia: A Children's Oncology Group study. Blood, 108(2), 711-717. https://doi.org/10.1182/blood-2006-02-002824

Biologic pathways associated with relapse in childhood acute lymphoblastic leukemia : A Children's Oncology Group study. / Bhojwani, Deepa; Kang, Huining; Moskowitz, Naomi P.; Min, Dong Joon; Lee, Hokyung; Potter, Jeffrey W.; Davidson, George; Willman, Cheryl L.; Borowitz, Michael J; Belitskaya-Levy, Ilana; Hunger, Stephen P.; Raetz, Elizabeth A.; Carroll, William L.

In: Blood, Vol. 108, No. 2, 15.07.2006, p. 711-717.

Research output: Contribution to journalArticle

Bhojwani, D, Kang, H, Moskowitz, NP, Min, DJ, Lee, H, Potter, JW, Davidson, G, Willman, CL, Borowitz, MJ, Belitskaya-Levy, I, Hunger, SP, Raetz, EA & Carroll, WL 2006, 'Biologic pathways associated with relapse in childhood acute lymphoblastic leukemia: A Children's Oncology Group study', Blood, vol. 108, no. 2, pp. 711-717. https://doi.org/10.1182/blood-2006-02-002824
Bhojwani, Deepa ; Kang, Huining ; Moskowitz, Naomi P. ; Min, Dong Joon ; Lee, Hokyung ; Potter, Jeffrey W. ; Davidson, George ; Willman, Cheryl L. ; Borowitz, Michael J ; Belitskaya-Levy, Ilana ; Hunger, Stephen P. ; Raetz, Elizabeth A. ; Carroll, William L. / Biologic pathways associated with relapse in childhood acute lymphoblastic leukemia : A Children's Oncology Group study. In: Blood. 2006 ; Vol. 108, No. 2. pp. 711-717.
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