Prochorec-Sobieszek Monika
aDepartment of Pathomorphology, Institute of Hematology and Transfusion Medicine, Poland bDepartment of Pathomorphology, Institute of Rheumatology, Warsaw, Poland.
Curr Opin Hematol. 2011 Jan;18(1):55-62. doi: 10.1097/MOH.0b013e328340dc12.
Large granular lymphocyte (LGL) syndrome comprises a clonal spectrum of T-cell and natural killer (NK)-cell LGL lymphoproliferative disorders associated with neutropenia. This review presents advances in diagnosis and therapy of LGL syndrome.
Due to the lack of a single unique genetic or phenotypic feature and clinicopathological overlap between reactive and neoplastic entities, accurate LGL syndrome diagnosis should be based on the combination of morphologic, immunophenotypic, and molecular studies as well as clinical features. For diagnosis and monitoring of LGL proliferations, it is essential to perform flow cytometric blood and/or bone marrow analysis using a panel of monoclonal antibodies to conventional and novel T-cell and NK-cell antigens such as NK-cell receptors and T-cell receptor β-chain variable region families together with TCR gene rearrangement studies. Treatment of symptomatic cytopenias in patients with indolent LGL leukemia is still based on immunosuppressive therapy. Treatment with purine analogs and alemtuzumab may be considered as an alternative option.
Progress in understanding the pathogenetic mechanisms of these entities, especially resistance of clonal LGLs to apoptosis, due to constitutive activation of survival signaling pathways, has its impact on identification of potential molecular therapeutic targets.
大颗粒淋巴细胞（LGL）综合征包括一系列与中性粒细胞减少相关的T细胞和自然杀伤（NK）细胞LGL淋巴增殖性疾病的克隆谱系。本综述介绍了LGL综合征诊断和治疗方面的进展。
由于缺乏单一独特的遗传或表型特征，以及反应性和肿瘤性实体之间的临床病理重叠，准确的LGL综合征诊断应基于形态学、免疫表型、分子研究以及临床特征的综合判断。对于LGL增殖的诊断和监测，使用一组针对传统和新型T细胞及NK细胞抗原（如NK细胞受体和T细胞受体β链可变区家族）的单克隆抗体进行流式细胞术血液和/或骨髓分析以及TCR基因重排研究至关重要。惰性LGL白血病患者有症状血细胞减少的治疗仍基于免疫抑制疗法。嘌呤类似物和阿仑单抗治疗可作为替代选择。
在理解这些实体的发病机制方面取得的进展，特别是由于生存信号通路的组成性激活导致克隆性LGL对凋亡的抵抗，对潜在分子治疗靶点的识别产生了影响。
