Department of Hematology, The Second Hospital of Lanzhou University, Lanzhou, China.
Stem Cell Immunity and Regeneration Key Laboratory of Luzhou, The Affiliated Hospital, Southwest Medical University, Luzhou, China.
Sci Rep. 2024 Jul 19;14(1):16711. doi: 10.1038/s41598-024-67067-w.
DARS, encoding for aspartyl-tRNA synthetase, is implicated in the pathogenesis of various cancers, including renal cell carcinoma, glioblastoma, colon cancer, and gastric cancer. Its role in BCR/ABL1-negative myeloproliferative neoplasms (MPNs), however, remains unexplored. This study aimed to elucidate the expression of DARS in patients with MPNs (PV 23, ET 19, PMF 16) through immunohistochemical analysis and to examine the profiles of circulating immune cells and cytokines using flow cytometry. Our findings indicate a significant overexpression of DARS in all MPNs subtypes at the protein level compared to controls (P < 0.05). Notably, elevated DARS expression was linked to splenomegaly in MPNs patients. The expression of DARS showed a negative correlation with CD4+ T cells (R = - 0.451, P = 0.0004) and CD4+ T/CD8+ T cell ratio (R = - 0.3758, P = 0.0040), as well as with CD68+ tumor-associated macrophages (R = 0.4037, P = 0.0017). Conversely, it was positively correlated with IL-2 (R = 0.5419, P < 0.001), IL-5 (R = 0.3161, P = 0.0166), IL-6 (R = 0.2992, P = 0.0238), and IFN-γ (R = 0.3873, P = 0.0029). These findings underscore a significant association between DARS expression in MPNs patients and specific clinical characteristics, as well as immune cell composition. Further investigation into the interplay between DARS and the immune microenvironment in MPNs could shed light on the underlying mechanisms of MPNs pathogenesis and immune dysregulation.
DARS 编码天冬氨酰-tRNA 合成酶，与各种癌症的发病机制有关，包括肾细胞癌、胶质母细胞瘤、结肠癌和胃癌。然而，其在 BCR/ABL1 阴性骨髓增生性肿瘤（MPNs）中的作用仍未被探索。本研究通过免疫组织化学分析旨在阐明 DARS 在 MPNs 患者（PV 23、ET 19、PMF 16）中的表达，并使用流式细胞术检查循环免疫细胞和细胞因子的特征。我们的研究结果表明，与对照组相比，所有 MPNs 亚型的 DARS 蛋白水平均显著过表达（P < 0.05）。值得注意的是，DARS 表达水平升高与 MPNs 患者的脾肿大有关。DARS 的表达与 CD4+T 细胞呈负相关（R = -0.451，P = 0.0004）和 CD4+T/CD8+T 细胞比值（R = -0.3758，P = 0.0040），以及与 CD68+肿瘤相关巨噬细胞（R = 0.4037，P = 0.0017）。相反，它与 IL-2（R = 0.5419，P < 0.001）、IL-5（R = 0.3161，P = 0.0166）、IL-6（R = 0.2992，P = 0.0238）和 IFN-γ（R = 0.3873，P = 0.0029）呈正相关。这些发现强调了 DARS 在 MPNs 患者中的表达与特定临床特征以及免疫细胞组成之间存在显著关联。进一步研究 DARS 与 MPNs 中免疫微环境之间的相互作用可能揭示 MPNs 发病机制和免疫失调的潜在机制。
