The role of UCH-L3 and LC3II in the diagnosis of acute myeloid leukemia

Abstract

Objective Todetect the mechanism of acute myeloid leukemia(AML) and the relationship between autophagy andubiquitin c-terminal hydrolases L3( UCH-L3) for providing new targets and guiding clinical management in AML. Methods 84 cases of AML patients and 25 controls were chosen from the First Affiliated Hospital of Dalian Medical University from 2014 to 2015, including 47 males and 37 females. The AML patients were divided into 3 groups : initialdiagnosis group[40 cases including 24 males and 16 females, with an median age of 54 (23-85)]; complete remission group[30 cases including 14 males and 16 females, with an median age of 45 (22-74)]and refractory group[14 cases including 9 males and 5 females, with an median age of 50 (18-80)]. Among those patients, there were 3 cases of M1, 42 cases of M2, 18 cases of M3, 3 cases of M4 and 18 cases of M5 subtypes.The expression of UCH-L3 and LC3II were detected by Real Time PCR and Western blot after the HL-60 cells were treated by TCID. The expression of UCH-L3 and LC3IIin the PBMC of AML patients and controls were detected with Real Time PCR. The expression levels of UCH-L3 and LC3II in different types of AML were analyzed. The relationship between the expression of LC3Ⅱand clinical features, clinical stages, laboratory results and therapeutic effects of patients were investigated. It further detected the expression of UCH-L3 and LC3IImRNA in post-induction status. t test were used for measurement data, χ2 test were performed for rate comparison; rank correlation test were performed for correlation analysis.Non-parametric test were performed for non-normal distribution data. Results Both the UCH-L3 and LC3 II were down-regulated after TCID treatment in HL-60 cellsat gene and protein levels (t=-29.435, t=-8.105, P<0.05). The expression of UCH-L3 in initial diagnosis group was lower than control group(Z=-3.87, P<0.05), butit was higher in remission group than initial diagnosis group and refractory group(Z=-6.70 , Z=-4.09, P<0.05). The expression level of LC3Ⅱin diagnosis group was significantly higher than control group, remission group and refractory group(Z=-6.96, Z=-5.32, Z=-3.52, P<0.05). Cytogenetic abnormalities in patients with high expression of LC3II were more common(χ2=6.510, P<0.05). The relative expression of UCH-L3 and LC3ⅡmRNA in the same patient before and after treatment were significantly different(P<0.05). During the remission, the expression of UCH-L3 was up-regulated compared with that before primary treatment, while the expression of LC3II was down-regulated. There was no statistically significant in the relative expression of UCH-L3 and LC3Ⅱamong the FAB type. Conclusion The UCH-L3 and autophagy are associated with pathogenesis of AML.(Chin J Lab Med, 2018, 41: 53-58) Key words: Leukemia, myeloid, acute; Cysteine endopeptidases; Microtubule-Associated Proteins; Autophagy