Hematologic Malignancy Branch, Division of Translational & Clinical Research II, Research Institute and Hospital, National Cancer Center, Gyeonggi-do, Republic of Korea.
Leuk Res. 2010 Sep;34(9):1127-31. doi: 10.1016/j.leukres.2009.11.028. Epub 2009 Dec 29.
BACKGROUND/AIMS: Lymphoma-specific gene expression in peripheral blood reflects the presence of circulating lymphoma cells (CLCs). MAGE-A3 is widely expressed in solid tumors and is a potent candidate for immunotherapy. To determine whether MAGE-A3 expression would be a useful marker for CLCs in non-Hodgkin lymphoma (NHL), we assessed MAGE-A3 mRNA expression in the peripheral blood of NHL patients and controls.
We measured MAGE-A3 gene expression in ten lymphoma cell lines (Farage, RL, SU-DHL, Toledo, WSU-NHL, BJA-B, Daudi, Raji, Granta-519 and Jurkat) using nested RT-PCR, and determined detection sensitivity using mixtures of MAGE-A3-positive and -negative cells over a range of 1/10(6) to 10(6)/10(6) cells. MAGE-A3 expression was determined in buffy coat samples of 40 controls and 95 NHL patients prior to treatment. Clinical characteristics (e.g., cell lineage) and international prognostic indices, including age, performance, LDH, stage and extra-nodal involvement, were evaluated and related to MAGE-A3 expression. Hazard ratios, reflecting risk for overall survival and progression-free survival, were also evaluated. Follow-up MAGE-A3 expression was evaluated at two time points: after 3-4 cycles of chemotherapy (80 patients) and after 6-8 cycles of chemotherapy (74 patients).
MAGE-A3 mRNA was detected in four lymphoma cell lines - RL, Farage, Toledo and Raji - and was present in 45 of 95 (47.3%) patients with NHL, but in none of the 40 controls. The detection sensitivity was 1 in 1000 cells. MAGE-A3 expression prior to treatment was not associated with clinical features or patient survival. During follow-up, only six patients (7.5%) were positive for MAGE-A3 after 3-4 cycles of chemotherapy and three (4.1%) were positive after 6-8 cycles.
The results showed that MAGE-A3 gene expression was frequent in NHL patients and decreased after effective chemotherapy, suggesting that MAGE-A3 can be used as a tumor marker for CLCs in patients with NHL. However, MAGE-A3 expression showed no prognostic value in this group of patients.
背景/目的：外周血中的淋巴瘤特异性基因表达反映了循环淋巴瘤细胞（CLCs）的存在。MAGE-A3 在实体肿瘤中广泛表达，是免疫治疗的有力候选者。为了确定 MAGE-A3 表达是否可作为非霍奇金淋巴瘤（NHL）中 CLCs 的有用标志物，我们评估了 NHL 患者和对照者外周血中的 MAGE-A3 mRNA 表达。
我们使用巢式 RT-PCR 测量了 10 种淋巴瘤细胞系（Farage、RL、SU-DHL、 Toledo、WSU-NHL、BJA-B、Daudi、Raji、Granta-519 和 Jurkat）中的 MAGE-A3 基因表达，并使用 1/10(6)至 10(6)/10(6)细胞范围的 MAGE-A3 阳性和阴性细胞混合物确定检测灵敏度。在治疗前，我们测定了 40 名对照者和 95 名 NHL 患者的 buffy coat 样本中的 MAGE-A3 表达。评估了临床特征（例如细胞谱系）和国际预后指数，包括年龄、表现、LDH、分期和结外累及，并将其与 MAGE-A3 表达相关联。还评估了反映总生存和无进展生存风险的危险比。在两个时间点评估了随访 MAGE-A3 表达：化疗 3-4 个周期后（80 名患者）和化疗 6-8 个周期后（74 名患者）。
MAGE-A3 mRNA 在四种淋巴瘤细胞系（RL、Farage、 Toledo 和 Raji）中被检测到，95 名 NHL 患者中有 45 名（47.3%）存在 MAGE-A3，但在 40 名对照者中均未检测到。检测灵敏度为 1/1000 细胞。治疗前的 MAGE-A3 表达与临床特征或患者生存无关。在随访期间，只有 6 名（7.5%）患者在化疗 3-4 个周期后 MAGE-A3 呈阳性，3 名（4.1%）患者在化疗 6-8 个周期后 MAGE-A3 呈阳性。
结果表明，MAGE-A3 基因表达在 NHL 患者中频繁发生，并在有效化疗后降低，提示 MAGE-A3 可用作 NHL 患者 CLCs 的肿瘤标志物。然而，在该组患者中，MAGE-A3 表达没有预后价值。
