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Objective: To investigate the genetic abnormality and protein expression of C-MYC and PD-L1 in the patients with ALK-negative anaplastic large cell lymphoma (ALK-ALCL), and to explore their roles in the pathogenesis of ALK-ALCL and their relationship with clinicopathological characteristics. Methods: Thirty-seven cases of ALK-ALCL diagnosed at Fujian Provincial Hospital from January 2003 to January 2017 were selected. Fluorescence in situ hybridization (FISH) was used to detect the genetic abnormality of C-MYC and PD-L1. The expression of C-MYC and PD-L1 proteins was detected by immunohistochemistry. The relationship between C-MYC and PD-L1 genes' abnormalities and protein expression was analyzed, as well as their associations with various clinicopathological parameters. Results: Among the 37 ALK-ALCL patients, 17 (45.9%) were positive for C-MYC protein, and 14 (37.8%) were positive for PD-L1 protein. There was a significant correlation between C-MYC protein and PD-L1 protein (r=0.990,P=0.014). The protein expression of C-MYC and PD-L1 (versus negative) was associated with the clinical stage of ALK-ALCL, respectively. The international prognosis index (IPI) in high-risk group was higher than that in the low-risk group (P<0.05). FISH test showed that 9 (24.3%) of the 37 cases had amplification of C-MYC gene, and no translocation of C-MYC gene was found in any of the cases. Amplification of PD-L1 gene was found in only 2 cases (5.4%). The 3-year overall survival rate of the C-MYC or PD-L1 immunohistochemistry-positive cases was significantly lower than those of the C-MYC or PD-L1 negative cases (P<0.01 and P<0.05), respectively. Conclusion: The expression of C-MYC and PD-L1 proteins are related to the clinical stage, IPI and overall survival rate of ALK-ALCL. Thus, it can be used to assess the disease's aggressiveness and to predict the prognosis of ALK-ALCL. The expression of PD-L1 in ALK-ALCL may be regulated by C-MYC, thus suggesting a possible design of combined C-MYC targeted therapy and immune checkpoint blocking for some ALK-ALCL patients.


C Wang, X Chen, X Y Chen, Z J You. Genetic abnormality and protein expression of C-MYC and PD-L1 in ALK-negative anaplastic large cell lymphoma]. Zhonghua bing li xue za zhi = Chinese journal of pathology. 2021 Jun 08;50(6):598-603

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PMID: 34078046

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