Stem Cell Center, Zhengzhou University School of Medicine, Zhengzhou 450001, China; Department of Pathology, Stanford University School of Medicine, Stanford 94305, CA.
Stem Cell Center, Zhengzhou University School of Medicine, Zhengzhou 450001, China.
Hum Pathol. 2014 May;45(5):1024-30. doi: 10.1016/j.humpath.2013.12.019. Epub 2014 Jan 21.
Staging for small B-cell lymphomas is important for prognostic and therapeutic decision making; however, the detection of lymphoid infiltrates in the bone marrow is often hampered by the lack of specific diagnostic markers. We recently described the hematopoietic tissue distribution patterns of CD137 and CD137 ligand (CD137L), which have shown promise as immunotherapeutic targets. CD137 expression was primarily confined to cells in the microenvironment, whereas CD137L was expressed in neoplastic cells in most B-cell lymphomas. Here we evaluate the use of CD137L in the detection of small B-cell lymphomas involving the bone marrow. To test the potential efficacy of CD137L in detecting bone marrow lymphoid infiltrates, 166 small B-cell lymphomas were evaluated by immunohistochemistry and double-immunofluorescence labeling on formalin-fixed, paraffin-embedded bone marrow core biopsies. CD137L was highly expressed in bone marrows involved by small B-cell lymphomas and included hairy cell leukemia, mantle cell lymphoma, follicular lymphoma, B-lymphoblastic leukemia, and chronic lymphocytic leukemia. In addition, a small subset of marginal zone lymphoma and most of lymphoplasmacytic lymphoma showed staining. Normal bone marrow cells including myeloid, erythroid and megakaryocytic precursors, and reactive lymphoid aggregates lacked staining. Our findings show that immunohistochemistry for CD137L is capable of reliably distinguishing small B-cell lymphomas from reactive lymphoid aggregates. These data also suggest that CD137L is useful in providing staging information for clinical diagnosis and is likely to furnish a potential target for minimal residual disease assessment as well as immunotherapy in patients with stage 4 disease.
小 B 细胞淋巴瘤的分期对于预后和治疗决策很重要；然而，骨髓中淋巴浸润的检测常常受到缺乏特异性诊断标志物的阻碍。我们最近描述了 CD137 和 CD137 配体（CD137L）的造血组织分布模式，它们作为免疫治疗靶点显示出了希望。CD137 表达主要局限于微环境中的细胞，而 CD137L 在大多数 B 细胞淋巴瘤中的肿瘤细胞中表达。在这里，我们评估了 CD137L 在检测骨髓受累的小 B 细胞淋巴瘤中的应用。为了测试 CD137L 在检测骨髓淋巴浸润中的潜在疗效，我们通过免疫组织化学和双免疫荧光标记对 166 例福尔马林固定、石蜡包埋的骨髓核心活检进行了评估。CD137L 在小 B 细胞淋巴瘤受累的骨髓中高度表达，包括毛细胞白血病、套细胞淋巴瘤、滤泡性淋巴瘤、B 淋巴母细胞白血病和慢性淋巴细胞白血病。此外，一小部分边缘区淋巴瘤和大多数淋巴浆细胞淋巴瘤也显示出染色。正常骨髓细胞包括髓系、红系和巨核细胞前体以及反应性淋巴聚集物缺乏染色。我们的研究结果表明，CD137L 的免疫组织化学能够可靠地区分小 B 细胞淋巴瘤与反应性淋巴聚集物。这些数据还表明，CD137L 有助于提供临床诊断的分期信息，并且可能为 4 期疾病患者的微小残留病评估以及免疫治疗提供潜在的靶标。
