The analysis of nuclear morphology plays an important role in glioma diagnosis and grading. We previously described intranuclear rods (rods) labeled with the SDL.3D10 monoclonal antibody against class III beta-tubulin (TUBB3) in human ependymomas. In a cohort of adult diffuse gliomas, we identified nuclear rods in 71.1% of IDH mutant lower-grade gliomas and 13.7% of IDH wild-type glioblastomas (GBMs). The presence of nuclear rods was associated with significantly longer postoperative survival in younger (≤65) GBM patients. Consistent with this, nuclear rods were mutually exclusive with Ki67 staining and their prevalence in cell nuclei inversely correlated with the Ki67 proliferation index. In addition, rod-containing nuclei showed a relative depletion of lamin B1, suggesting a possible association with senescence. To gain insight into their functional significance, we addressed their antigenic properties. Using a TUBB3-null mouse model, we demonstrate that the SDL.3D10 antibody does not bind TUBB3 in rods but recognizes an unknown antigen. In the present study, we show that rods show immunoreactivity for the nucleotide synthesizing enzymes inosine monophosphate dehydrogenase (IMPDH) and cytidine triphosphate synthetase. By analogy with the IMPDH filaments that have been described previously, we postulate that rods regulate the activity of nucleotide-synthesizing enzymes in the nucleus by sequestration, with important implications for glioma behavior.

中文翻译：

---

人神经胶质瘤中的核 IMPDH 丝

核形态分析在神经胶质瘤的诊断和分级中起着重要作用。我们之前描述了在人室管膜瘤中用针对 III 类 β-微管蛋白 (TUBB3) 的 SDL.3D10 单克隆抗体标记的核内杆 (杆)。在一组成人弥漫性胶质瘤中，我们在 71.1% 的 IDH 突变低级别胶质瘤和 13.7% 的 IDH 野生型胶质母细胞瘤 (GBM) 中发现了核棒。核棒的存在与年轻 (≤65) GBM 患者术后生存期显着延长有关。与此一致，核棒与 Ki67 染色相互排斥，并且它们在细胞核中的流行与 Ki67 增殖指数呈负相关。此外，含杆状细胞核显示核纤层蛋白 B1 相对耗尽，表明可能与衰老有关。为了深入了解它们的功能意义，我们解决了它们的抗原特性。使用 TUBB3 缺失小鼠模型，我们证明 SDL.3D10 抗体不结合视杆细胞中的 TUBB3，但识别未知抗原。在本研究中，我们发现杆对核苷酸合成酶肌苷一磷酸脱氢酶 (IMPDH) 和胞苷三磷酸合成酶显示出免疫反应性。通过与之前描述的 IMPDH 丝类比，我们假设杆状体通过螯合调节细胞核中核苷酸合成酶的活性，这对神经胶质瘤行为具有重要意义。在本研究中，我们发现杆对核苷酸合成酶肌苷一磷酸脱氢酶 (IMPDH) 和胞苷三磷酸合成酶显示出免疫反应性。通过与之前描述的 IMPDH 丝类比，我们假设杆状体通过螯合调节细胞核中核苷酸合成酶的活性，这对神经胶质瘤行为具有重要意义。在本研究中，我们发现杆对核苷酸合成酶肌苷一磷酸脱氢酶 (IMPDH) 和胞苷三磷酸合成酶显示出免疫反应性。通过与之前描述的 IMPDH 丝类比，我们假设杆状体通过螯合调节细胞核中核苷酸合成酶的活性，这对神经胶质瘤行为具有重要意义。