Giatromanolaki Alexandra, Koukourakis Michael I, Pouliliou Stamatia, Gatter Kevin C, Pezzella Francesco, Harris Adrian L, Sivridis Efthimios
Department of Pathology, Democritus University of Thrace Medical School, University General Hospital of Alexandroupolis, Alexandroupolis 68100, Greece.
Hematol Oncol Stem Cell Ther. 2013 Mar;6(1):20-5. doi: 10.1016/j.hemonc.2013.02.001. Epub 2013 Feb 28.
Autophagy is a self-degradation mechanism induced under stress conditions in all eukaryotic cells. Its activity in human lymphomas has not been studied as yet.
In this study, the autophagic activity of lymphoid cells was investigated in follicular lymphomas (FL; 48 cases), diffuse large B-cell lymphomas (DLBCL; 78 cases), and in reactive follicular hyperplasias (41 cases), using the light chain 3A (LC3A) antibody and a standard immunohistochemical technique.
In all cases, the pattern of LC3A reactivity was uniformly diffuse cytoplasmic, but expressed more frequently in FLs (68.8%) than in DLBCLs (41%) (p=0.02), and much more commonly in DLBCLs than in reactive lymph nodes (24.3%) (p<0.006). Interestingly, FLs expressing LC3A in >10% of lymphoid cells (high reactivity) were associated with the hypoxia-related protein HIF1α and the enzyme of anaerobic metabolism lactate dehydrogenase LDH5 (p=0.004 and p=0.003, respectively). Such associations, however, were not a feature in DLBCLs of increased LC3A activity.
LC3A expression in FLs is hypoxia-induced, whereas its expression in DLBCLs may be regulated by other molecular mechanisms. The current study provides a tool for further assessment of autophagic activity in translational and autophagy targeting therapy studies.
自噬是所有真核细胞在应激条件下诱导产生的一种自我降解机制。其在人类淋巴瘤中的活性尚未得到研究。
在本研究中，使用轻链3A（LC3A）抗体和标准免疫组织化学技术，对滤泡性淋巴瘤（FL；48例）、弥漫性大B细胞淋巴瘤（DLBCL；78例）和反应性滤泡增生（41例）中的淋巴细胞自噬活性进行了研究。
在所有病例中，LC3A反应模式均为均匀的弥漫性细胞质，但在FLs（68.8%）中比在DLBCLs（41%）中更频繁表达（p = 0.02），且在DLBCLs中比在反应性淋巴结（24.3%）中更常见（p < 0.006）。有趣的是，在>10%的淋巴细胞中表达LC3A（高反应性）的FLs与缺氧相关蛋白HIF1α和无氧代谢酶乳酸脱氢酶LDH5相关（分别为p = 0.004和p = 0.003）。然而，这种关联在LC3A活性增加的DLBCLs中并非特征。
FLs中LC3A表达是由缺氧诱导的，而其在DLBCLs中的表达可能受其他分子机制调控。本研究为进一步评估自噬活性提供了一种工具，用于转化研究和自噬靶向治疗研究。
