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

被引:131
作者
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.
机构
[1] NYU, Div Pediat Hematol Oncol, Ctr Canc, New York, NY 10016 USA
[2] NYU, Sch Med, Dept Biostat, New York, NY USA
[3] Mt Sinai Sch Med, Dept Pediat, New York, NY USA
[4] Univ New Mexico, Canc Res & Treatment Ctr, Albuquerque, NM 87131 USA
[5] Sandia Natl Labs, Albuquerque, NM 87185 USA
[6] Univ Florida, Coll Med, Dept Pediat, Gainesville, FL USA
[7] Univ Florida, Shands Canc Ctr, Gainesville, FL USA
[8] Johns Hopkins Med Inst, Dept Pathol & Oncol, Baltimore, MD 21205 USA
关键词
D O I
10.1182/blood-2006-02-002824
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:711 / 717
页数:7
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