Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
PLoS One. 2013 Aug 14;8(8):e70812. doi: 10.1371/journal.pone.0070812. eCollection 2013.
Interferon regulatory factor 8 (IRF8) is a transcription factor that plays a critical role in normal hematopoiesis, such that disruption of IRF8 activity promotes leukemogenesis. We and others have identified aberrant expression of IRF8 transcripts, including novel splice variants, in acute myeloid leukemia (AML), but studies have not investigated the prognostic significance of these transcripts. Therefore, we developed and optimized quantitative expression assays for both, the wild type, or the reference sequence (WT-IRF8) and novel splice variants (SV-IRF8). These assays were used to quantify IRF8 transcript levels in 194 adult patients with AML, and multivariate analyses investigated the prognostic significance of these expression levels. After adjusting for known prognostic factors, expression levels of WT- or SV-IRF8 transcripts were not significantly associated with complete responses or overall survival. However, increased expression of WT-IRF8 was associated with decreased relapse-free survival (RFS) in both univariate (P = 0.010) and multivariate (P = 0.019) analyses. Similarly, increased expression of SV-IRF8 was associated with a decreased RFS (univariate, P = 0.026 and multivariate, P = 0.021). These studies show for the first time that WT-IRF8 and SV-IRF8 are independent adverse prognostic factors for patients with AML. Additional studies are planned to examine the prognostic significance of IRF8 transcripts in other populations of AML patients.
干扰素调节因子 8（IRF8）是一种转录因子，在正常造血中起着关键作用，因此，IRF8 活性的破坏会促进白血病的发生。我们和其他人已经在急性髓系白血病（AML）中发现了 IRF8 转录本的异常表达，包括新的剪接变异体，但这些研究尚未探讨这些转录本的预后意义。因此，我们开发并优化了用于野生型或参考序列（WT-IRF8）和新型剪接变异体（SV-IRF8）的定量表达检测。这些检测用于定量分析 194 例成人 AML 患者的 IRF8 转录本水平，并进行多变量分析以探讨这些表达水平的预后意义。在调整已知的预后因素后，WT-或 SV-IRF8 转录本的表达水平与完全缓解或总生存率均无显著相关性。然而，WT-IRF8 表达水平的增加与无复发生存率（RFS）的降低有关（单变量，P=0.010；多变量，P=0.019）。同样，SV-IRF8 表达水平的增加与 RFS 的降低有关（单变量，P=0.026；多变量，P=0.021）。这些研究首次表明，WT-IRF8 和 SV-IRF8 是 AML 患者的独立不良预后因素。计划进行更多研究以检验 IRF8 转录本在其他 AML 患者群体中的预后意义。
