caArray_krahe-00060: Expression profiling reveals fundamental biological differences in acute myeloid leukemia

Acute myeloid leukemia (AML) is a heterogeneous group of diseases. Normal cytogenetics (CN) constitutes the single largest group, while trisomy 8 (+8) as a sole abnormality is the most frequent trisomy. How trisomy contributes to tumorigenesis is unknown. We used oligonucleotide-based DNA microarrays to study global gene expression in AML+8 patients with +8 as the sole chromosomal abnormality and AML-CN patients. CD34+ cells purified from normal bone marrow (BM) were also analyzed as a representative heterogeneous population of stem and progenitor cells. Expression patterns of AML patients were clearly distinct from those of CD34+ cells of normal individuals. We show that AML+8 blasts overexpress genes on chromosome 8, estimated at 32% on average, suggesting gene-dosage effects underlying AML+8. Systematic analysis by cellular function indicated up-regulation of genes involved in cell adhesion in both groups of AML compared with CD34+ blasts from normal individuals. Perhaps most interestingly, apoptosis-regulating genes were significantly down-regulated in AML+8 compared with AML-CN. We conclude that the clinical and cytogenetic heterogeneity of AML is due to fundamental biological differences. **NOTE: Migrated from caArray 1.x, identifier='gov.nih.nci.ncicb.caarray:Experiment:1015897559579654:1' krahe-00060 Assay Type: Gene Expression Provider: Affymetrix Array Designs: Hu6800 Organism: Homo sapiens (ncbitax) Tissue Sites: Bone marrow Material Types: synthetic_DNA, synthetic_RNA, organism_part Cell Types: Myeloid Cell Disease States: Acute Myeloid Leukemia, Normal

急性髓系白血病（Acute myeloid leukemia, AML）是一类异质性疾病群。正常核型（normal cytogenetics, CN）是其中占比最高的单一亚型，而仅伴有8号染色体三体（trisomy 8, +8）的病例是最常见的三体异常类型。目前关于8号染色体三体促进肿瘤发生的具体机制仍不明确。
本研究采用基于寡核苷酸的DNA微阵列技术，对仅伴有8号染色体三体的AML（AML+8）患者以及正常核型AML（AML-CN）患者的全基因组基因表达谱进行了分析。同时，我们还对从正常骨髓（bone marrow, BM）中纯化得到的CD34+细胞进行了分析，以此作为干细胞与祖细胞异质性群体的代表样本。
AML患者的基因表达谱与正常个体的CD34+细胞存在显著差异。
本研究发现，AML+8患者的白血病原始细胞在8号染色体上的基因表达平均上调约32%，提示AML+8的发病机制可能与基因剂量效应相关。
通过细胞功能类别开展的系统性分析显示，与正常个体的CD34+原始细胞相比，两类AML患者样本中参与细胞黏附过程的基因均出现上调。
尤为值得关注的是，与AML-CN患者相比，AML+8患者样本中调控细胞凋亡的基因出现了显著下调。
综上，本研究认为急性髓系白血病的临床与细胞遗传学异质性源于其内在的根本性生物学差异。
**注：本数据集从caArray 1.x平台迁移而来，标识符为'gov.nih.nci.ncicb.caarray:Experiment:1015897559579654:1'，项目编号为krahe-00060。检测类型：基因表达；提供商：Affymetrix；芯片设计：Hu6800；物种：智人（ncbitax）；组织采集部位：骨髓；材料类型：合成DNA、合成RNA、机体组织；细胞类型：髓系细胞；疾病状态：急性髓系白血病、正常**