Division of Hematology, Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
Int J Hematol. 2012 Oct;96(4):461-8. doi: 10.1007/s12185-012-1159-x. Epub 2012 Aug 14.
Mature natural killer (NK)-cell neoplasms include extranodal NK/T cell lymphoma, nasal type (ENKL), aggressive NK-cell leukemia (ANKL) and chronic lymphoproliferative disorders of NK cells (CLPD-NK). Granulysin, a cytolytic granule protein, is expressed in cytotoxic T cells and NK cells, and is found in the sera as well, and functions as a cytotoxic and proinflammatory protein. Cytolytic proteins, such as granzyme B and perforin, have been shown to play crucial pathophysiological roles in NK/T cell neoplasms and have also been utilized for diagnostic purposes. Granulysin in NK-cell proliferative disorders, however, has yet to be fully analyzed. To elucidate the clinical relevance of granulysin in mature NK-cell neoplasms, we measured serum granulysin and analyzed cytolytic molecules immunohistologically. The median concentrations of serum granulysin were 39.0, 2.85, 2.8 and 1.35 ng/ml in ANKL, ENKL, CLPD-NK and healthy subjects, respectively (P < 0.01). Serum granulysin was significantly elevated in patients with ANKL compared with the levels in ENKL (P = 0.006) and CLPD-NK (P = 0.037). Furthermore, serum granulysin was correlated with whole-blood EBV viral load in ENKL and ANKL (P = 0.005) and was significantly reduced after treatment. Different expression patterns of cytolytic granule proteins were observed among the mature NK-cell neoplasms. Granulysin is closely associated with the characteristics of NK-cell neoplasms and serum granulysin may serve as a novel biomarker for these disorders.
成熟自然杀伤 (NK) 细胞肿瘤包括结外 NK/T 细胞淋巴瘤，鼻型（ENKL），侵袭性 NK 细胞白血病（ANKL）和慢性 NK 细胞淋巴组织增生性疾病（CLPD-NK）。颗粒酶 B 和穿孔素等细胞毒性蛋白已被证明在 NK/T 细胞肿瘤中发挥关键的病理生理作用，并且也被用于诊断目的。然而，NK 细胞增殖性疾病中的颗粒酶 B 尚未得到充分分析。为了阐明颗粒酶 B 在成熟 NK 细胞肿瘤中的临床相关性，我们测量了血清颗粒酶 B 并通过免疫组织化学分析了细胞毒性分子。ANKL、ENKL、CLPD-NK 和健康受试者的血清颗粒酶 B 浓度中位数分别为 39.0、2.85、2.8 和 1.35ng/ml（P<0.01）。与 ENKL（P=0.006）和 CLPD-NK（P=0.037）相比，ANKL 患者的血清颗粒酶 B 显著升高。此外，血清颗粒酶 B 与 ENKL 和 ANKL 中的全血 EBV 病毒载量相关（P=0.005），并且在治疗后显著降低。成熟 NK 细胞肿瘤中观察到细胞毒性颗粒蛋白的不同表达模式。颗粒酶 B 与 NK 细胞肿瘤的特征密切相关，血清颗粒酶 B 可能成为这些疾病的新型生物标志物。
