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
New York University (NYU) Cancer Institute and Division of Pediatric Hematology/Oncology, NY 10016, USA.
Blood. 2006 Jul 15;108(2):711-7. doi: 10.1182/blood-2006-02-002824.
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.
儿童急性淋巴细胞白血病（ALL）复发后的预后较差。为深入了解复发机制，我们使用Affymetrix平台分析了35对匹配的诊断/复发样本以及60例复发时接受统一治疗的儿童的基因表达谱。配对分析显示，诊断样本与早期复发样本在细胞周期调控、DNA修复和凋亡相关基因的表达上存在显著差异。这些通路中有许多先前已被证明与肿瘤发生有关，是干预策略的有吸引力的靶点。相比之下，晚期复发样本对之间未观察到共同的变化模式。早期复发样本更有可能与其各自的诊断样本相似，而我们注意到晚期复发样本对之间的基因表达模式差异更大。早期复发与晚期复发样本的表达谱比较表明，早期复发克隆的特征是与细胞周期调控相关的生物学通路过度表达。这些结果表明，早期复发是由一个相关克隆的出现导致的，其特征是介导细胞增殖的基因上调。相比之下，晚期复发似乎由多种通路介导。
