Progranulin is a novel independent predictor of disease progression and overall survival in chronic lymphocytic leukemia.
Progranulin is a novel independent predictor of disease progression and overall survival in chronic lymphocytic leukemia.
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预熟蛋白是慢性淋巴细胞性白血病的疾病进展和总体存活的新型独立预测指标。
DOI：
10.1371/journal.pone.0072107
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Dürig J
中科院分区：
文献类型：
--
作者：
Göbel M;Eisele L;Möllmann M;Hüttmann A;Johansson P;Scholtysik R;Bergmann M;Busch R;Döhner H;Hallek M;Seiler T;Stilgenbauer S;Klein-Hitpass L;Dührsen U;Dürig J
颗粒蛋白前体（Progranulin，Pgrn）是一种分子量为88 kDa的分泌性蛋白质，具有调节细胞周期进程、细胞运动、创伤修复和肿瘤发生等多种功能。使用基于微阵列的基因表达谱，我们最近证明了Pgrn基因，颗粒蛋白（GRN），在侵袭性CD 38 +ZAP-70+中的表达显著高于惰性CD 38 − ZAP-70−慢性淋巴细胞白血病（CLL）病例。在此，我们通过酶联免疫吸附试验（ELISA）测定了131例埃森CLL队列患者的Pgrn血浆浓度，并检查了Pgrn与已建立的预后标志物和临床结果的相关性。我们发现高Pgrn血浆水平与不良风险因素密切相关，包括未突变的IGHV状态，CD 38和ZAP-70的表达，荧光原位杂交（FISH）检测到的不良风险细胞遗传学（11 q-，17 p-）和高Binet分期。Pgrn以及上述危险因素是该系列中首次治疗时间和总生存期的预后因素。重要的是，这些结果可以在未经治疗的Binet A期患者的独立多中心CLL 1队列（n = 163）中得到证实。 在此，首次治疗时间的多变量分析显示，高风险Pgrn（HR = 2.06，95%-CI = 1.13-3.76，p = 0.018）、未突变IGHV状态（HR = 5.63，95%-CI = 3.05-10.38，p<0.001）、研究方案定义的高风险（HR = 2.06，95%-CI = 1.09-3.89，p = 0.026）而非低风险细胞遗传学是独立的预后标志物。 总之，我们的研究结果表明，Pgrn是一种新的，强大的和独立的预后标志物，在CLL，可以很容易地通过ELISA测量。
Progranulin (Pgrn) is a 88 kDa secreted protein with pleiotropic functions including regulation of cell cycle progression, cell motility, wound repair and tumorigenesis. Using microarray based gene expression profiling we have recently demonstrated that the gene for Pgrn, granulin (GRN), is significantly higher expressed in aggressive CD38+ZAP-70+ as compared to indolent CD38−ZAP-70− chronic lymphocytic leukemia (CLL) cases. Here, we measured Pgrn plasma concentrations by enzyme-linked immunosorbent assay (ELISA) in the Essen CLL cohort of 131 patients and examined Pgrn for association with established prognostic markers and clinical outcome. We found that high Pgrn plasma levels were strongly associated with adverse risk factors including unmutated IGHV status, expression of CD38 and ZAP-70, poor risk cytogenetics (11q-, 17p-) as detected by flourescence in situ hybridization (FISH) and high Binet stage. Pgrn as well as the aforementioned risk factors were prognostic for time to first treatment and overall survival in this series. Importantly, these results could be confirmed in the independent multicentric CLL1 cohort of untreated Binet stage A patients (n = 163). Here, multivariate analysis of time to first treatment revealed that high risk Pgrn (HR = 2.06, 95%-CI = 1.13–3.76, p = 0.018), unmutated IGHV status (HR = 5.63, 95%-CI = 3.05–10.38, p<0.001), high risk as defined by the study protocol (HR = 2.06, 95%-CI = 1.09–3.89, p = 0.026) but not poor risk cytogenetics were independent prognostic markers. In summary our results suggest that Pgrn is a novel, robust and independent prognostic marker in CLL that can be easily measured by ELISA.
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