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Objective: To analyze the clinicopathological characteristics of 11 cases of chronic lymphocytic leukemia (CLL) with t (14;19) (q32;q13) . Methods: The case data of 11 patients with CLL with t (14;19) (q32;q13) in the chromosome karyotype analysis results of the Blood Diseases Hospital, Chinese Academy of Medical Sciences from January 1, 2018, to July 30, 2022, were retrospectively analyzed. Results: In all 11 patients, t (14;19) (q32;q13) involved IGH::BCL3 gene rearrangement, and most of them were accompanied by +12 or complex karyotype. An immunophenotypic score of 4-5 was found in 7 patients and 3 in 4 cases. We demonstrated that CLLs with t (14;19) (q32;q13) had a mutational pattern with recurrent mutations in NOTCH1 (3/7), FBXW7 (3/7), and KMT2D (2/7). The very-high-risk, high-risk, intermediate-risk, and low-risk groups consisted of 1, 1, 6, and 3 cases, respectively. Two patients died, 8 survived, and 2 were lost in follow-up. Four patients had disease progression or relapse during treatment. The median time to the first therapy was 1 month. Conclusion: t (14;19) (q32;q13), involving IGH::BCL3 gene rearrangement, is a rare recurrent cytogenetic abnormality in CLL, which is associated with a poor prognosis.
Subject(s)
Humans , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Retrospective Studies , Translocation, Genetic , Chromosome Aberrations , KaryotypingABSTRACT
Objective:To investigate the effects of Bcl3 gene knockout on the composition of spleen immune cells and antitumor ability of mice.Methods:Bcl3 gene knockout mice (Bcl3 -/-) were established by CRISPR/Cas9 genome editing technology. Blood routine test and flow cytometry were used to detect the immune cell composition in Bcl3 -/- mice. Lung metastasis models were established by injecting mice with B16F10 melanoma cells. The number of tumor nodules in lung and the survival time of mice were used to assess the antitumor ability of wild-type (WT) and Bcl3 -/- mice. Results:Bcl3 -/- mice were successfully bred to a strain with normal growth rate and normal breeding performance. Furthermore, no embryonic death occurred. Compared with WT mice, Bcl3 -/- mice showed splenomegaly and a significant increase in the number of spleen immune cells ( P<0.05). The counts and percentages of platelets and neutrophils in Bcl3 -/- mice were significantly lower than those in WT mice. The proportion of CD19 + B cells showed no significant change, while the proportions of CD3 + T cells and T cell subsets (CD4 + , CD8 + , Treg) increased significantly ( P<0.05). The proportions of NK cells (NK1.1 + ) and neutrophils (Gr1 + ) decreased ( P<0.05), while no significant change in the proportion of DC (CD11b + ) was observed. There were a large number of tumor nodules formed by melanoma cells in the lung of Bcl3 -/- tumor bearing mice, and their survival time was shortened dramatically. Conclusions:Knockout of Bcl3 gene affected the development, differentiation and function of immune cells, thereby reducing the antitumor ability of mice.
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PURPOSE: Gastric cancer is a highly metastatic malignant tumor, often characterized by chemoresistance and high mortality. In the present study, we aimed to investigate the role of B-cell lymphoma 3 (Bcl-3) protein on cell migration and chemosensitivity of gastric cancer.MATERIALS AND METHODS: The gastric cancer cell lines, AGS and NCI-N87, were used for the in vitro studies and the in vivo studies were performed using BALB/c nude mice. Western blotting, wound healing assay, Cell Counting Kit-8 assay, immunohistochemistry, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay were used to evaluate the role of Bcl-3 in gastric cancer.RESULTS: We found that the protein expression of hypoxia (HYP)-inducible factor-1α and Bcl-3 were markedly upregulated under hypoxic conditions in both AGS and NCI-N87 cells in a time-dependent manner. Interestingly, small interfering RNA-mediated knockdown of Bcl-3 expression affected the migration and chemosensitivity of the gastric cancer cells. AGS and NCI-N87 cells transfected with si-RNA-Bcl-3 (si-Bcl-3) showed significantly reduced migratory ability and increased chemosensitivity to oxaliplatin, 5-fluorouracil, and irinotecan. In addition, si-Bcl-3 restored the autophagy induced by HYP. Further, the protective role of si-Bcl-3 on the gastric cancer cells could be reversed by the autophagy inducer, rapamycin. Importantly, the in vivo xenograft tumor experiments showed similar results.CONCLUSIONS: Our present study reveals that Bcl-3 knockdown inhibits cell migration and chemoresistance of gastric cancer cells through restoring HYP-induced autophagy.
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AIM:To investigate the effects of bcl-3 gene on the migration and apoptosis of human colon cancer cell line RKO, and the changes of cyclin D1 and apoptosis-related proteins.METHODS:After silencing of bcl-3 gene expression in human colon cancer cell line RKO by lentiviral vector with RNA interference, the changes of RKO cell migration ability were investigated by wound healing assay.The changes of RKO cell apoptotic rate after bcl-3 gene silencing were detected by flow cytometry with Annexin V/PI staining.The protein expression of cyclin D1 and apoptosis-related proteins in the RKO cells after bcl-3 gene silencing was determined by Western blot.RESULTS:The wound healing rates of the RKO cells were 84.00% and 40.00% before and after bcl-3 gene silencing, respectively, with statistically significant difference (P<0.05).Annexin V/PI staining showed that the cell apoptotic rates were 12.89% and 59.67% before and after bcl-3 gene silencing, respectively, when RKO cells were treated with 5 μmol/L cisplatin for 24 h, with statistically significant difference (P<0.05).The expression of cyclin D1 decreased, while the expression of Bax increased after bcl-3 gene silencing (P<0.05).CONCLUSION:After bcl-3 gene silencing, the migration ability of RKO cells decreases, and the apoptotic rate increases, accompanying with the changes of cyclin D1 and Bax.bcl-3 gene can affect the apoptosis of RKO cells by changing the expression of cyclin D1 and Bax.
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OBJECTIVES: Isolated cleft lip with or without cleft palate (CL/P) is among the most common human birth defects, with a prevalence of approximately 1 in 700 live births. The B-Cell Leukemia/lymphoma 3 (BCL3) gene has been suggested as a candidate gene for CL/P based on association and linkage studies in some populations. This study tests for an association between markers in BCL3 and isolated, non-syndromic CL/P using a case-parent trio design, while considering parent-of-origin effects. METHODS: Forty case-parent trios were genotyped for two single nucleotide polymorphisms (SNPs) in the BCL3 gene. We performed a transmission disequilibrium test (TDT) on individual SNPs, and the FAMHAP package was used to estimate haplotype frequencies and to test for excess transmission of multi-SNP haplotypes. RESULTS: The odds ratio for transmission of the minor allele, OR (transmission), was significant for SNP rs8100239 (OR=3.50, p=0.004) and rs2965169 (OR=2.08, p=0.027) when parent-of-origin was not considered. Parent-specific TDT revealed that SNP rs8100239 showed excess maternal transmission. Analysis of haplotypes of rs2965169 and rs8100239 also suggested excess maternal transmission. CONCLUSIONS: BCL3 appears to influence risk of CL/P through a parent-of-origin effect with excess maternal transmission.
Subject(s)
Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Male , Young Adult , Algorithms , Alleles , Chi-Square Distribution , Chromosomes, Human, Pair 19/genetics , Cleft Lip/genetics , Cleft Palate/genetics , Genetic Markers , Genetic Predisposition to Disease , Genotype , Haplotypes , Korea , Monte Carlo Method , Odds Ratio , Polymorphism, Single Nucleotide/genetics , Risk FactorsABSTRACT
Tumor suppressor CYLD is a deubiquitination enzyme that could regulate NF-?B and JNK signal pathways by deubiquitinating TRAFs,NEMO,Bcl-3 and p53,and in turn regulating the cell cycle and apoptosis.Loss or deficiency of CYLD would lead to the development of skin tumor,including multiple familial trichoepithelioma(MFT),familial cylindromatosis(FC),Brooke-Spiegler syndrome(BSS).Cancers like uterine cervix,kidney,and colon and hepatocellular carcinoma are related to the down-regulation of CYLD.