Kontos Christos K, Papageorgiou Sotirios G, Diamantopoulos Marios A, Scorilas Andreas, Bazani Efthimia, Vasilatou Diamantina, Gkontopoulos Konstantinos, Glezou Eirini, Stavroulaki Georgia, Dimitriadis George, Pappa Vasiliki
Second Department of Internal Medicine and Research Unit, University General Hospital "Attikon", 1 Rimini St., Haidari, 12462 Athens, Greece; Department of Biochemistry and Molecular Biology, National and Kapodistrian University of Athens, Panepistimiopolis, 15701 Athens, Greece.
Second Department of Internal Medicine and Research Unit, University General Hospital "Attikon", 1 Rimini St., Haidari, 12462 Athens, Greece.
Leuk Res. 2017 Feb;53:65-73. doi: 10.1016/j.leukres.2016.11.014. Epub 2016 Nov 29.
The hypoxia inducible factor 1 (HIF1) is a heterodimeric transcription factor that ultimately regulates cellular responses to changes in oxygen tension. In this study, we examined the potential diagnostic and prognostic potential of the mRNA expression of HIF1 regulatory α-subunit (HIF1A) in chronic lymphocytic leukemia (CLL). For this purpose, total RNA was isolated from peripheral blood mononuclear cells collected from 88 CLL patients and 33 non-leukemic blood donors, and poly(A)-RNA was reversely transcribed. HIF1A mRNA levels were quantified using real-time PCR. Kaplan-Meier survival analysis showed that high HIF1A mRNA expression predicts inferior overall survival for CLL patients (p=0.001). Bootstrap univariate Cox regression analysis confirmed that HIF1A mRNA overexpression is a significant unfavorable prognosticator in CLL (hazard ratio=3.75, bias-corrected and accelerated 95% confidence interval=1.43-24.36, bootstrap p<0.001), independent of other established prognostic factors, including CD38 expression, the mutational status of the immunoglobulin heavy chain variable region (IGHV), and the clinical stage (Binet or Rai stage) or risk group (p<0.001 in all cases). Interestingly, HIF1A mRNA positivity retains its unfavorable prognostic value in distinct subgroups of patients, stratified according to established prognostic factors. Thus, HIF1A mRNA overexpression can be regarded as a promising, independent molecular biomarker of unfavorable prognosis in CLL.
缺氧诱导因子1（HIF1）是一种异二聚体转录因子，最终调节细胞对氧张力变化的反应。在本研究中，我们检测了HIF1调节性α亚基（HIF1A）的mRNA表达在慢性淋巴细胞白血病（CLL）中的潜在诊断和预后价值。为此，从88例CLL患者和33例非白血病献血者采集的外周血单个核细胞中分离总RNA，并将poly(A)-RNA进行逆转录。使用实时PCR定量HIF1A mRNA水平。Kaplan-Meier生存分析表明，高HIF1A mRNA表达预示CLL患者的总生存期较差（p = 0.001）。自抽样单变量Cox回归分析证实，HIF1A mRNA过表达是CLL中一个显著的不良预后因素（风险比 = 3.75，偏差校正和加速95%置信区间 = 1.43 - 24.36，自抽样p < 0.001），独立于其他已确立的预后因素，包括CD38表达、免疫球蛋白重链可变区（IGHV）的突变状态以及临床分期（Binet或Rai分期）或风险组（所有情况下p < 0.001）。有趣的是，根据已确立的预后因素分层，HIF1A mRNA阳性在不同患者亚组中仍保留其不良预后价值。因此，HIF1A mRNA过表达可被视为CLL中一个有前景的、独立的不良预后分子生物标志物。
