Kuo Sung-Hsin, Cheng Ann-Lii
Departments of 1Oncology and.
Hematology Am Soc Hematol Educ Program. 2013;2013:109-17. doi: 10.1182/asheducation-2013.1.109.
Low-grade mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach, gastric MALT lymphoma, is associated with Helicobacter pylori infection. The eradication of H pylori using antibiotics is successful in 60% to 80% of affected patients. In contrast to the previous paradigm, we and other investigators have shown that a certain proportion of patients with H pylori-positive early-stage diffuse large B-cell lymphoma (DLBCL) of the stomach with histological evidence of MALT lymphoma, including high-grade transformed gastric MALT lymphoma and gastric DLBCL(MALT), achieved long-term complete pathological remission (pCR) after first-line H pylori eradication therapy, indicating that the loss of H pylori dependence and high-grade transformation are separate events in the progression of gastric lymphoma. In addition, patients with H pylori-positive gastric DLBCL without histological evidence of MALT (gastric pure DLBCL) may also respond to H pylori eradication therapy. A long-term follow-up study showed that patients who achieved pCR remained lymphoma free. Gastric MALT lymphoma is indirectly influenced by H pylori infection through T-cell stimulation, and recent studies have shown that H pylori-triggering chemokines and their receptors, H pylori-associated epigenetic changes, H pylori-regulated miRNA expression, and tumor infiltration by CD4+CD25+ regulatory T cells contribute to lymphomagenesis of gastric MALT lymphoma. Recent studies have also demonstrated that the translocation of CagA into B lymphocytes inhibits apoptosis through p53 accumulation, BAD phosphorylation, and the up-regulation of Bcl-2 and Bcl-XL expression. In gastric MALT lymphoma, CagA may stimulate lymphomagenesis directly, through the regulation of signal transduction, and intracellular CagA is associated with H pylori dependence. These findings represent a substantial paradigm shift compared with the classical theory of H pylori-reactive T cells contributing indirectly to the development of MALT lymphoma. In conclusion, a wide range of H pylori-related gastric lymphomas have been identified. The use of antibiotics as the sole first-line therapy for early-stage gastric pure DLBCL requires validation in a prospective study. The clinical and biological significance of the CagA oncoprotein in the lymphomagenesis of gastric MALT lymphoma warrants further study.
胃低度黏膜相关淋巴组织（MALT）淋巴瘤，即胃MALT淋巴瘤，与幽门螺杆菌感染有关。使用抗生素根除幽门螺杆菌在60%至80%的受影响患者中取得成功。与之前的模式不同，我们和其他研究者已表明，一定比例的幽门螺杆菌阳性早期胃弥漫性大B细胞淋巴瘤（DLBCL）患者，其组织学表现为MALT淋巴瘤，包括高级别转化型胃MALT淋巴瘤和胃DLBCL（MALT），在一线幽门螺杆菌根除治疗后实现了长期完全病理缓解（pCR），这表明幽门螺杆菌依赖性丧失和高级别转化在胃淋巴瘤进展中是独立事件。此外，无MALT组织学证据的幽门螺杆菌阳性胃DLBCL患者（胃纯DLBCL）也可能对幽门螺杆菌根除治疗有反应。一项长期随访研究表明，实现pCR的患者无淋巴瘤复发。胃MALT淋巴瘤通过T细胞刺激受到幽门螺杆菌感染的间接影响，最近的研究表明，幽门螺杆菌引发的趋化因子及其受体、幽门螺杆菌相关的表观遗传变化、幽门螺杆菌调节的miRNA表达以及CD4 + CD25 +调节性T细胞的肿瘤浸润都有助于胃MALT淋巴瘤的发生。最近的研究还表明，CagA转位至B淋巴细胞通过p53积累、BAD磷酸化以及Bcl - 2和Bcl - XL表达上调抑制细胞凋亡。在胃MALT淋巴瘤中，CagA可能通过调节信号转导直接刺激淋巴瘤发生，且细胞内CagA与幽门螺杆菌依赖性有关。与幽门螺杆菌反应性T细胞间接促成MALT淋巴瘤发生的经典理论相比，这些发现代表了重大的模式转变。总之，已确定了多种与幽门螺杆菌相关的胃淋巴瘤。将抗生素作为早期胃纯DLBCL的唯一一线治疗方法需要在前瞻性研究中进行验证。CagA癌蛋白在胃MALT淋巴瘤发生中的临床和生物学意义值得进一步研究。
