Department of Clinical Laboratory, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Department of Medical Oncology, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Biomed Res Int. 2018 Nov 11;2018:1042597. doi: 10.1155/2018/1042597. eCollection 2018.
Activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is a common subtype of non-Hodgkin's lymphoma and is very likely to infiltrate the bone marrow. Over 30% of patients are converted to relapsed/refractory DLBCL after first-line rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, with a poor prognosis. Our aim was to identify molecular markers that might be utilized to predict relapsed/refractory ABC-DLBCL patients. Hence, we collected bone marrow aspirate smears from 202 patients with ABC-DLBCL and detected expression of bone marrow molecular marker proteins by immunocytochemistry. Signal transducer and activator of transcription (Stat)3, nuclear factor (NF)-B p65, Syk, Bruton's tyrosine kinase (BTK), and Bcl2 proteins were strongly expressed in bone marrow aspirate smears of ABC-DLBCL patients. The same smear could present positive expression of multiple proteins simultaneously. Positive combinations of protein expression were associated with resistance. The most significant finding was that the Stat3NF-B group developed resistance, which was significantly higher than that of the Stat3NF-Bgroup (80 vs. 14%). There was a significant difference in two-year relapse-free survival between protein-positive and protein-negative combinations of Stat3-NF-B (P = 0.005), Bcl2-Stat3 (P = 0.009), Bcl2-Pax5 (P = 0.003), and BTK-Syk (P < 0.001). Thus, we detected key molecules in multiple signaling pathways in bone marrow aspirate smears. At the same time, the results provide further clinical evidence of ABC-DLBCL drug-resistant molecules and provide a theoretical basis for rational second-line treatment after drug resistance.
生发中心 B 细胞样弥漫性大 B 细胞淋巴瘤（ABC-DLBCL）是一种常见的非霍奇金淋巴瘤亚型，很可能浸润骨髓。超过 30%的患者在接受一线利妥昔单抗联合环磷酰胺、多柔比星、长春新碱和泼尼松治疗后转化为复发/难治性 DLBCL，预后较差。我们的目的是确定可能用于预测复发/难治性 ABC-DLBCL 患者的分子标志物。因此，我们收集了 202 例 ABC-DLBCL 患者的骨髓抽吸涂片，并通过免疫细胞化学检测骨髓分子标志物蛋白的表达。信号转导和转录激活因子（Stat）3、核因子（NF）-B p65、Syk、布鲁顿酪氨酸激酶（BTK）和 Bcl2 蛋白在 ABC-DLBCL 患者的骨髓抽吸涂片中强烈表达。同一张涂片可能同时呈现多种蛋白的阳性表达。蛋白表达的阳性组合与耐药性有关。最显著的发现是 Stat3-NF-B 组发生耐药，明显高于 Stat3-NF-B 组（80%比 14%）。Stat3-NF-B（P=0.005）、Bcl2-Stat3（P=0.009）、Bcl2-Pax5（P=0.003）和 BTK-Syk（P<0.001）蛋白阳性和蛋白阴性组合之间的两年无复发生存率有显著差异。因此，我们在骨髓抽吸涂片中检测到多个信号通路中的关键分子。同时，这些结果为 ABC-DLBCL 耐药分子提供了进一步的临床证据，并为耐药后合理的二线治疗提供了理论依据。
