Qiu Zhi-Yuan, Fan Yu
Department of Oncology, The Affiliated People's Hospital of Jiangsu University, Zhenjiang 212002, Jiangsu Province, China. E-mail:
Department of Oncology, The Affiliated People's Hospital of Jiangsu University, Zhenjiang 212002, Jiangsu Province, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2016 Feb;24(1):254-60. doi: 10.7534/j.issn.1009-2137.2016.01.049.
Large granular lymphocytic leukemia (LGLL) is a rare lymphoproliferative disorder of clonal expansion of cytotoxic T- or NK-cells in blood and bone marrow, and often associated with autoimmune disorders. According to the current WHO classification of the hematopoietic and lymphoid tissue tumors, the clonal LGL expansions are further classified as T-cell large granular lymphocytic leukemia (T-LGLL), chronic lymphoproliferative disorders of NK cells (CLPD-NK) and aggressive NK cell leukemia. Since there is a general lack of awareness of this disease, some patients may be misdiagnosed or some cases may be missed when diagnosis was done. At present, the pathogenesis of LGLL remains incomplete and unclear, and the therapeutic effects are unsatisfactory. For this reason, it is necessary to find prognostic marks and therapeutic targets of this disease. The constitutive activation of JAK/STAT pathway has been claimed to be involved in the development of LGLL. Recently, the somatic mutations in the SH2 domain of STAT3 in LGLL are frequently observed, which lead to the activation of JAK/STAT pathway. STAT3 is the first molecular markers that are highly specific for LGLL, and STAT3 mutations have been rarely detected in other tumor types studied, thus the STAT3 mutations can be used as molecular markers for LGLL diagnosis and can provide a novel therapeutic target for patients with LGLL.
大颗粒淋巴细胞白血病（LGLL）是一种罕见的淋巴细胞增殖性疾病，由血液和骨髓中的细胞毒性T细胞或NK细胞克隆性扩增引起，常与自身免疫性疾病相关。根据世界卫生组织目前对造血和淋巴组织肿瘤的分类，克隆性LGL扩增进一步分为T细胞大颗粒淋巴细胞白血病（T-LGLL）、NK细胞慢性淋巴细胞增殖性疾病（CLPD-NK）和侵袭性NK细胞白血病。由于对这种疾病普遍缺乏认识，一些患者可能被误诊，或者在诊断时一些病例可能被漏诊。目前，LGLL的发病机制仍不完全清楚，治疗效果也不尽人意。因此，有必要寻找该疾病的预后标志物和治疗靶点。JAK/STAT通路的组成性激活被认为与LGLL的发生发展有关。最近，在LGLL中经常观察到STAT3的SH2结构域发生体细胞突变，从而导致JAK/STAT通路的激活。STAT3是首个对LGLL具有高度特异性的分子标志物，在其他研究的肿瘤类型中很少检测到STAT3突变，因此STAT3突变可作为LGLL诊断的分子标志物，并可为LGLL患者提供新的治疗靶点。
