ten Berge Rosita L, Oudejans Joost J, Ossenkoppele Gert J, Meijer Chris J L M
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
J Pathol. 2003 May;200(1):4-15. doi: 10.1002/path.1331.
Anaplastic large cell lymphoma (ALCL) can be divided into two major groups. The first is a spectrum of CD30+ T-cell lymphoproliferative disorders including primary cutaneous ALCL and lymphomatoid papulosis, usually affecting older patients but characterized by an excellent prognosis. The second is systemic nodal ALCL, which on the basis of genetic and immunophenotypic features combined with clinical parameters can be divided into two subgroups: anaplastic lymphoma kinase (ALK)-positive and ALK-negative systemic ALCL. ALK expression, usually the result of a t(2;5) translocation, correlates with the expression of other markers such as EMA and a cytotoxic phenotype, and is strongly related to younger age groups, lower international prognostic index (IPI) risk groups, and a good prognosis. ALK-negative ALCL, however, shows a more heterogeneous immunophenotype and clinical behaviour, and prognostic parameters are needed to determine treatment strategies in individual patients. Besides clinical parameters included in the IPI, recent studies have pointed out several biological prognosticators of potential value, such as the percentage of tumour-infiltrating activated cytotoxic T-lymphocytes. The expression of proteins involved in the execution or regulation of apoptosis, such as activated caspase 3, Bcl-2, and PI9, was also found to be strongly related to clinical outcome. These studies indicate that inhibition of the apoptosis cascade in particular is an important mechanism that can explain the poor clinical outcome in therapy refractory ALCL. Functional studies are required to investigate whether disruption of one or more of the apoptosis pathways is the major factor in the fatal outcome of the disease and whether apoptosis resistance based on inhibition of one pathway can be overcome by activating another pathway that is still intact.
间变性大细胞淋巴瘤（ALCL）可分为两大组。第一组是一系列CD30+ T细胞淋巴增殖性疾病，包括原发性皮肤ALCL和淋巴瘤样丘疹病，通常影响老年患者，但预后良好。第二组是系统性淋巴结ALCL，根据基因和免疫表型特征结合临床参数可分为两个亚组：间变性淋巴瘤激酶（ALK）阳性和ALK阴性系统性ALCL。ALK表达通常是t(2;5)易位的结果，与其他标志物如EMA的表达和细胞毒性表型相关，并且与较年轻年龄组、较低的国际预后指数（IPI）风险组以及良好的预后密切相关。然而，ALK阴性ALCL表现出更异质的免疫表型和临床行为，需要预后参数来确定个体患者的治疗策略。除了IPI中包含的临床参数外，最近的研究还指出了几个具有潜在价值的生物学预后指标，如肿瘤浸润活化细胞毒性T淋巴细胞的百分比。还发现参与凋亡执行或调节的蛋白质表达，如活化的半胱天冬酶3、Bcl-2和PI9，与临床结果密切相关。这些研究表明，特别是凋亡级联反应的抑制是一个重要机制，可以解释治疗难治性ALCL的不良临床结果。需要进行功能研究来调查一条或多条凋亡途径的破坏是否是该疾病致命结局的主要因素，以及基于一条途径抑制的凋亡抗性是否可以通过激活另一条仍然完整的途径来克服。
