Whole-blood transcriptional profiling of interferon-inducible genes identifies highly upregulated IFI27 in primary myelofibrosis
Whole-blood transcriptional profiling of interferon-inducible genes identifies highly upregulated IFI27 in primary myelofibrosis
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DOI：
10.1111/j.1600-0609.2011.01618.x
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发表时间：
2011-07-01
影响因子：
3.1
通讯作者：
Hasselbalch, Hans Carl
中科院分区：
文献类型：
--
作者：
Skov, Vibe;Larsen, Thomas Stauffer;Hasselbalch, Hans Carl
基因表达谱研究揭示了几个基因的失调，这些基因可能对费城阴性慢性骨髓增殖性肿瘤的发展和表型具有重要的致病作用。在干扰素-α2 作为一种有前途的治疗药物的背景下，我们重点研究了原发性血小板增多症 (ET) (n = 19)、真性红细胞增多症 (PV) (n = 41) 和原发性骨髓纤维化 (PMF) (n = 9) 患者的干扰素相关基因的转录谱。使用全血转录分析并相应地获得在几种免疫细胞（粒细胞、单核细胞、B细胞、T细胞、血小板）中表达的基因的整合特征，我们已经鉴定出许多干扰素相关基因显着失调，但干扰素诱导基因27（IFI27）（ET、PV和PMF，倍数变化分别为8、16和30）高度显着失调。 IFI 基因的显着失调可能反映出晚期骨髓纤维化患者的免疫系统受到过度刺激但不足，其中 IFI27 基因表现出极高的表达。干扰素特征可能反映原发性骨髓纤维化是慢性炎症的倦怠阶段，由于夸大但无能的抗肿瘤免疫反应，最终引发克隆进化和扩张。最后，IFI27 可能是 CMPN 患者疾病活动性和肿瘤负荷的新型生物标志物。
Gene expression profiling studies have unraveled deregulation of several genes that might be of pathogenetic importance for the development and phenotype of the Philadelphia-negative chronic myeloproliferative neoplasms. In the context of interferon-alpha2 as a promising therapeutic agent, we focused upon the transcriptional profiling of interferon-associated genes in patients with essential thrombocythemia (ET) (n = 19), polycythemia vera (PV) (n = 41), and primary myelofibrosis (PMF) (n = 9). Using whole-blood transcriptional profiling and accordingly obtaining an integrated signature of genes expressed in several immune cells (granulocytes, monocytes, B cells, T cells, platelets), we have identified a number of interferon-associated genes to be significantly deregulated but with a highly significant deregulation of interferon-inducible gene 27 (IFI27) (ET, PV, and PMF, fold change 8, 16, and 30, respectively). The striking deregulation of IFI genes may reflect a hyperstimulated but insufficient immune system being most enhanced in patients with advanced myelofibrosis, in whom the IFI27 gene displayed an exceedingly high expression. The interferon signature may reflect primary myelofibrosis as the burn-out phase of chronic inflammation which ultimately elicits clonal evolution and expansion owing to an exaggerated but incompetent antitumor immune response. Finally, IFI27 may be a novel biomarker of disease activity and tumor burden in patients with CMPNs.