Department of Clinical Genetics.
Leuk Lymphoma. 2013 Oct;54(10):2269-73. doi: 10.3109/10428194.2013.764417. Epub 2013 May 15.
Gene expression profiling studies in the Philadelphia-negative chronic myeloproliferative neoplasms have revealed significant deregulation of several immune and inflammation genes that might be of importance for clonal evolution due to defective tumor immune surveillance. Other mechanisms might be down-regulation of major histocompatibility (MHC) class I and II genes, which are used by tumor cells to escape antitumor T-cell-mediated immune responses. We have performed whole blood transcriptional profiling of genes encoding human leukocyte antigen (HLA) class I and II molecules, β2-microglobulin and members of the antigen processing machinery of HLA class I molecules (LMP2, LMP7, TAP1, TAP2 and tapasin). The findings of significant down-regulation of several of these genes may possibly be of major importance for defective tumor immune surveillance. Since up-regulation of HLA genes is recorded during treatment with epigenome modulating agents (DNA-hypomethylators and DNA-hyperacetylators [histone deacetylase inhibitors]) and interferon-α2, our findings call for prospective transcriptional studies of HLA genes during treatment with these agents.
费城阴性慢性骨髓增殖性肿瘤的基因表达谱研究表明,由于肿瘤免疫监视缺陷,几个免疫和炎症基因的表达出现显著失调,这可能对克隆进化很重要。其他机制可能是主要组织相容性(MHC)I 类和 II 类基因的下调,肿瘤细胞利用这些基因逃避抗肿瘤 T 细胞介导的免疫反应。我们对编码人类白细胞抗原(HLA)I 类和 II 类分子、β2-微球蛋白和 HLA I 类分子抗原加工机制成员(LMP2、LMP7、TAP1、TAP2 和 tapasin)的基因进行了全血转录谱分析。这些基因的表达下调可能对肿瘤免疫监视缺陷具有重要意义。由于在表观基因组调节剂(DNA 低甲基化剂和 DNA 高乙酰化剂[组蛋白去乙酰化酶抑制剂])和干扰素-α2 治疗期间记录到 HLA 基因的上调,我们的发现呼吁在这些药物治疗期间对 HLA 基因进行前瞻性转录研究。