Unidad de Investigación Médica en Epidemiología Clínica, UMAE Hospital de Pediatría, Centro Médico Nacional (CMN) "Siglo XXI", Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico.
Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico.
Arch Med Res. 2016 Nov;47(8):644-655. doi: 10.1016/j.arcmed.2016.12.005.
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer worldwide. Mexican patients have high mortality rates, low frequency of good prognosis biomarkers (i.e., ETV6-RUNX1) and a high proportion is classified at the time of diagnosis with a high risk to relapse according to clinical features. In addition, very early relapses are more frequently observed than in other populations. The aim of the study was to identify new potential biomarkers associated with very early relapse in Mexican ALL children through transcriptome analysis.
Microarray gene expression profiling on bone marrow samples of 54 pediatric ALL patients, collected at time of diagnosis and/or at relapse, was performed. Eleven patients presented relapse within the first 18 months after diagnosis. Affymetrix Human Transcriptome Array 2.0 (HTA 2.0) was used to perform gene expression analysis. Annotation and functional enrichment analyses were carried out using Gene Ontology, KEGG pathway analysis and Ingenuity Pathway Analysis tools.
BLVRB, ZCCHC7, PAX5, EBF1, TMOD1 and BLNK were differentially expressed (fold-change >2.0 and p value <0.01) between relapsed and non-relapsed patients. Functional analysis of abnormally expressed genes revealed their important role in cellular processes related to the development of hematological diseases, cancer, cell death and survival and in cell-to-cell signaling interaction.
Our data support previous findings showing the relevance of PAX5, EBF1 and ZCCHC7 as potential biomarkers to identify a subgroup of ALL children in high risk to relapse.
急性淋巴细胞白血病（ALL）是全世界儿童中最常见的癌症。墨西哥患者的死亡率较高，预后良好的生物标志物（如 ETV6-RUNX1）频率较低，且在诊断时根据临床特征，很大一部分患者被归类为高复发风险。此外，与其他人群相比，非常早期的复发更为常见。本研究旨在通过转录组分析，确定与墨西哥 ALL 儿童非常早期复发相关的新潜在生物标志物。
对 54 例儿科 ALL 患者的骨髓样本进行微阵列基因表达谱分析，这些样本分别在诊断时和/或复发时采集。11 例患者在诊断后 18 个月内复发。使用 Affymetrix Human Transcriptome Array 2.0（HTA 2.0）进行基因表达分析。使用基因本体论、KEGG 通路分析和 Ingenuity Pathway Analysis 工具进行注释和功能富集分析。
BLVRB、ZCCHC7、PAX5、EBF1、TMOD1 和 BLNK 在复发和未复发患者之间的表达存在差异（倍数变化>2.0，p 值<0.01）。异常表达基因的功能分析表明，它们在与血液系统疾病、癌症、细胞死亡和存活以及细胞间信号相互作用相关的细胞过程中具有重要作用。
我们的数据支持先前的研究结果，表明 PAX5、EBF1 和 ZCCHC7 作为潜在的生物标志物，可用于识别高复发风险的 ALL 儿童亚群。
