Objective: To explore the prognostic value of circulating tumor DNA (ctDNA) testing in patients with refractory/relapsed diffuse large B-cell lymphoma (R/R DLBCL) undergoing chimeric antigen receptor T-cell (CAR-T) therapy, and to guide the prevention and subsequent treatment of CAR-T-cell therapy failure. Methods: In this study, 48 patients with R/R DLBCL who received CAR-T-cell therapy at the First Affiliated Hospital of Zhejiang University School of Medicine between December 2017 and March 2022 were included. Furthermore, ctDNA testing of 187 lymphoma-related gene sets was performed on peripheral blood samples obtained before treatment. The patients were divided into complete remission and noncomplete remission groups. The chi-square test and t-test were used to compare group differences, and the Log-rank test was used to compare the differences in survival. Results: Among the patients who did not achieve complete remission after CAR-T-cell therapy for R/R DLBCL, the top ten genes with the highest mutation frequencies were TP53 (41%), TTN (36%), BCR (27%), KMT2D (27%), IGLL5 (23%), KMT2C (23%), MYD88 (23%), BTG2 (18%), MUC16 (18%), and SGK1 (18%). Kaplan-Meier survival analysis revealed that patients with ctDNA mutation genes >10 had poorer overall survival (OS) rate (1-year OS rate: 0 vs 73.8%, P<0.001) and progression-free survival (PFS) rate (1-year PFS rate: 0 vs 51.8%, P=0.011) compared with patients with ctDNA mutation genes ≤10. Moreover, patients with MUC16 mutation positivity before treatment had better OS (2-year OS rate: 56.8% vs 26.7%, P=0.046), whereas patients with BTG2 mutation positivity had poorer OS (1-year OS rate: 0 vs 72.5%, P=0.005) . Conclusion: ctDNA detection can serve as a tool for evaluating the efficacy of CAR-T-cell therapy in patients with R/R DLBCL. The pretreatment gene mutation burden, mutations in MUC16 and BTG2 have potential prognostic value.
Humans ; Prognosis ; Receptors, Chimeric Antigen ; Circulating Tumor DNA/genetics* ; Feasibility Studies ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Lymphoma, Non-Hodgkin ; Mutation ; Cell- and Tissue-Based Therapy ; Retrospective Studies ; Immediate-Early Proteins ; Tumor Suppressor Proteins

OBJECTIVE: To investigate the relationships between caspase-8 (CASP8), fatty acid synthetase (Fas) gene polymorphisms and prognosis of non-Hodgkin's lymphoma patients in Han nationality. METHODS: The clinical data of 85 patients with non-Hodgkin's lymphoma were analyzed retrospectively. The polymorphisms of CASP8 and Fas gene were detected, and prognosis of the patients were analyzed. The polymorphisms of CASP8 and Fas gene in patients with different prognosis were compared, and the relationships between gene polymorphisms and the poor prognosis of the patients were investigated. RESULTS: The incidence rate of poor prognosis of the patients enrolled in the study was 65.88%. The polymorphisms of CASP8 and Fas genes in the patients with poor or good prognosis were in accordance with Hardy Weinberg's law of genetic balance. The frequencies of GG genotype and G allele at rs 1035142 of CASP8 gene, GA genotype and A allele at rs 1377 of Fas gene in patients with poor prognosis were lower than those of the patients with good prognosis (P<0.05). The frequencies of GT, TT and T alleles at rs 1035142 of CASP8 gene, GG and G alleles at rs 1377 of Fas gene in patients with poor prognosis were higher than those of the patients with good prognosis (P<0.05). The proportions of Ann Arbor stage III-IV and high malignancy in patients with poor prognosis were higher than those of the patients with good prognosis (P<0.05). Logistic multiple regression analysis showed that Ann Arbor stage III-IV, moderate malignant, high malignancy, CASP8 rs 1035142 GT genotype, CASP8 rs 1035142 TT genotype and Fas rs 1377 GG genotype were all the risk factors for the poor prognosis of the patients (P<0.05). CONCLUSION The poor prognosis rate of non-Hodgkin's lymphoma patients in Han nationality is relatively high, and the risk factors for the prognosis of the patients include Ann Arbor stage III-IV, moderate and high malignancy, CASP8 rs 1035142 GT genotype, CASP8 rs 1035142 TT genotype and Fas rs 1377 GG genotype.
Caspase 8/genetics* ; Ethnicity ; Fatty Acids ; Humans ; Ligases ; Lymphoma, Non-Hodgkin/genetics* ; Polymorphism, Genetic ; Prognosis ; Retrospective Studies ; fas Receptor

OBJECTIVE: To investigate the effect of lncRNA-CASC2 (CASC2) /miR-155-5p/APC axis to the progression of non-Hodgikn lymphoma (NHL). METHODS: The expression level of CASC2 and miR-155-5p in NHL cell lines were examined by qRT-PCR. Dual-luciferase reporter gene assay was used to verify the relationship between miR-155-5p, CASC2 and APC. The effects of CASC/miR-155-5p/APC axis to the proliferation, invasion and apoptosis of NK-92 cells were detected by MTT, Transwell assay and flow cytometry assay, respectively. RESULTS: CASC2 was downregulated in NHL cell lines. Overexpression of CASC2 could inhibit the proliferation and invasion of NK-92 cells, and promote its apoptosis. Dual-luciferase reporter gene assay confirmed that there was a targeting relationship between miR-155-5p, CASC2 and APC. The restoration experiments proved that knockdown of both miR-155-5p and CASC2 or APC could restore the inhibitory effect of miR-155-5p silencing to the biological behavior of NK-92 cells. CONCLUSION Overexpression of CASC2 suppresses the proliferation and invasion of NK-92 cells, promote the apoptosis of NK-92 cells via targeting miR-155-5p and upregulating APC expression.
Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphoma, Non-Hodgkin/genetics* ; MicroRNAs/genetics* ; RNA, Long Noncoding/genetics* ; Tumor Suppressor Proteins/genetics*

OBJECTIVETo investigate the role of cytogenetic analysis in the detection of bone marrow (BM) involvement in patients with non-Hodgkin's lymphoma (NHL).

METHODSThe bone marrow samples of 74 patients with NHL were detection by using morphology, cytogenetic test, flow cytometry and molecular biological assay. The detected results of morphology, cytogenetic test, flow cytometry and molecular biological assay alone and thier combined detection were compared, the detective rate and consistencies of the 4 methods were analyzed.

RESULTSThe detection rates of BM involvement by using morphology, cytogenetic, flow cytometry, and molecular biological assays were 21.6%, 17.6%, 23.0% and 33.8% respectively. The detective rate was enhanced to 44.6% by combining the 4 methods. Cytogenetic test showed the result consistent with the other methods.

CONCLUSIONAlthough cytogenetic test shows a lower detective rate than the other methods, but in some patients the cytogenetic test can detect the abnormality of bone marrow which can not be detected by other methods alone, the combination test of 4 detection methods can enhance the detectable rate of BM involvement.

Bone Marrow ; pathology ; Bone Marrow Examination ; Cytogenetic Analysis ; Flow Cytometry ; Humans ; Lymphoma, Non-Hodgkin ; diagnosis ; genetics

OBJECTIVETo explore the clinical values of detecting immunophenotype and analyzing DNA ploid by flow cytometry for patients with non-Hogkin's lymphoma (NHL).

METHODSEighty NHL patients admitted in our hospital from August 2007 years to March 2015 Years were included in the observation group, 20 patients with reactive lymphoid hyperplasias were selectod as control group. The immunophenotypes were detected and the DNA ploid was analyzed by flow cytometry.

RESULTSThe detected rate of DNA aneuploidy, DAN index (DI) and SPF in observation group were higher than those in control group, there was signifificant difference (P < 0.05). The SPF and DI in patients with NHL-I, NHL-II had no statistical difference as compared with that in control group (P > 0.05); but the SPF and DI in pateints with NHL-III and patients with NHL-IV showed statistical significance as compared with that in control group (P < 0.05). The SPF and DI in patients with low malignancy group and middle malignancy group showed statistical significance as compared with control group (P < 0.05). The SPF and DI in middle malignancy group had statistical significance as compared with that in low malignancy group (P < 0.05).

CONCLUSIONthe immunophenotype detection and DNA ploid analysis by flow cytometry can reflect the tumor proliferation and deterioration of patients with Non-Hogkin's lymphoma, predicting the prognosis.

Aneuploidy ; Case-Control Studies ; DNA ; Flow Cytometry ; Humans ; Immunophenotyping ; Lymphoma, Non-Hodgkin ; classification ; genetics ; Ploidies ; Prognosis

To determine expression of lactate dehydrogenase (LDH)-5 in non-Hodgkin lymphoma and its clinical significance.
 Methods: LDH-5 levels and LDH levels in NHL patients were examined by agarose gel electrophoresis and enzymatic method (n=63), respectively. Positive rates of LDH-5 and LDH were statistically analyzed.
 Results: The median age of NHL patients was 56(19-84) years old, including 36 males and 27 females. The positive numbers for LDH-5 and LDH in the initial treatment group (n=43) were significantly different (P<0.05). There was significant difference in 22 cases of diffuse large B cell lymphoma and in 9 cases of T cell lymphoma, whereas there was not significant difference in 12 cases of small B cell lymphoma (P>0.05). In 15 cases under the status of progress, the difference of LDH-5 and LDH expressions were not significant (P>0.05), whereas the difference in cases of small B cell lymphoma was significant (P<0.05).
 Conclusion: LDH-5 can be used as an index for NHL to judge the tumor load and to predict the recurrence.
Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; blood ; metabolism ; Female ; Humans ; Isoenzymes ; metabolism ; L-Lactate Dehydrogenase ; metabolism ; Lactate Dehydrogenase 5 ; Lymphoma, B-Cell ; genetics ; Lymphoma, Large B-Cell, Diffuse ; genetics ; Lymphoma, Non-Hodgkin ; genetics ; Lymphoma, T-Cell ; genetics ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; genetics ; Prognosis ; Tumor Burden

To explore the role of the special AT rich sequence binding protein-1 (SATB1) and ribonucleotide reductase M2 (RRM2) in enhancing malignant progression of non-Hodgkin lymphoma (NHL). 
 Methods: A total of 42 NHL and 42 chronic lymphadenitis patients were recruited. The protein expressions of SATB1 and RRM2 in cervical lymph nodes were determined by Western blot. After overexpression of SATB1, siSATB1 or siRRM2, the mRNA levels of SATB1 and RRM2 in cells were analyzed via RT-PCR, the cell proliferation was evaluated via MTT and EdU assays, while the migration and invasion of cells were assessed by transwell assays.
 Results: Compared with chronic lymphadenitis, the expressions of SATB1 and RRM2 in NHL patients were up-regulated. There was positive correlation between SATB1 and RRM2 in NHL patients. RRM2 mRNA level was up-regulated after transfection of SATB1 and down-regulated after transfection of siSATB1. Overexpression of SATB1 increased tumor cell proliferation, migration and invasion, while knockdown of RRM2 reversed those phenomena.
 Conclusion: SATB1 functions as an oncogene and promotes tumor cell proliferation, migration and invasion by up-regulation of RRM2 in NHL.
Cell Cycle Proteins ; genetics ; physiology ; Cell Movement ; genetics ; Cell Proliferation ; genetics ; Down-Regulation ; Gene Expression Regulation, Neoplastic ; genetics ; Humans ; Lymph Nodes ; chemistry ; Lymphoma, Non-Hodgkin ; Matrix Attachment Region Binding Proteins ; genetics ; physiology ; Neoplasm Invasiveness ; genetics ; Oncogenes ; genetics ; physiology ; RNA, Messenger ; RNA, Small Interfering ; Ribonucleoside Diphosphate Reductase ; Ribonucleotide Reductases ; genetics ; physiology ; Signal Transduction ; Transcription Factors ; Transcriptional Activation ; Transfection ; Tumor Cells, Cultured ; Up-Regulation

BACKGROUNDSerine hydroxymethyltransferase 1 (SHMT1) is a key enzyme in the folate metabolic pathway that plays an important role in biosynthesis by providing one carbon unit. SHMT1 C1420T may lead to the abnormal biosynthesis involved in DNA synthesis and methylation, and it may eventually increase cancer susceptibility. Many epidemiologic studies have explored the association between C1420T polymorphism and the risk of non-Hodgkin lymphoma (NHL), but the results have been contradictory. Therefore, we performed this meta-analysis to evaluate the relationship.

METHODSThe meta-analyses were conducted to evaluate the effect of SHMT1 C1420T polymorphism on NHL risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure the strength of the association.

RESULTSEight studies encompassing 3232 cases and 4077 controls were included. A statistically significant association was found between SHMT1 C1420T polymorphism and NHL risk under the allelic comparison (T vs. C: OR = 1.09, 95% CI 1.01-1.17); a borderline association was found between SHMT1 C1420T polymorphism and NHL risk under the homozygote model (TT vs. CC: OR = 1.18, 95% CI 1.00-1.39) and the dominant model (CT+TT vs. CC: OR = 1.10, 95% CI 1.00-1.21).

CONCLUSIONSHMT1 C1420T polymorphism may be associated with NHL risk, which needs to be validated in large, prospective studies.

Case-Control Studies ; Evidence-Based Medicine ; methods ; Genetic Predisposition to Disease ; Glycine Hydroxymethyltransferase ; genetics ; Humans ; Lymphoma, Non-Hodgkin ; genetics ; Neoplasm Proteins ; genetics ; Polymorphism, Single Nucleotide ; Publication Bias ; Sensitivity and Specificity

Acute graft-versus-host disease (aGVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the mechanisms of aGVHD are not well understood. We aim to investigate the roles of the three angiogenic factors: angiopoietin-1 (Ang-1), Ang-2 and vascular endothelial growth factor (VEGF) in the development of aGVHD. Twenty-one patients who underwent allo-HSCT were included in our study. The dynamic changes of Ang-1, Ang-2 and VEGF were monitored in patients before and after allo-HSCT. In vitro, endothelial cells (ECs) were treated with TNF-β in the presence or absence of Ang-1, and then the Ang-2 level in the cell culture medium and the tubule formation by ECs were evaluated. After allo-HSCT, Ang-1, Ang-2 and VEGF all exhibited significant variation, suggesting these factors might be involved in the endothelial damage in transplantation. Patients with aGVHD had lower Ang-1 level at day 7 but higher Ang-2 level at day 21 than those without aGVHD, implying that Ang-1 may play a protective role in early phase yet Ang-2 is a promotion factor to aGVHD. In vitro, TNF-β promoted the release of Ang-2 by ECs and impaired tubule formation of ECs, which were both weakened by Ang-1, suggesting that Ang-1 may play a protective role in aGVHD by influencing the secretion of Ang-2, consistent with our in vivo tests. It is concluded that monitoring changes of these factors following allo-HSCT might help to identify patients at a high risk for aGVHD.
Acute Disease ; Adolescent ; Adult ; Angiogenesis Inducing Agents ; immunology ; metabolism ; pharmacology ; Angiopoietin-1 ; genetics ; immunology ; pharmacology ; Angiopoietin-2 ; genetics ; immunology ; pharmacology ; Antineoplastic Agents ; therapeutic use ; Female ; Gene Expression Regulation, Neoplastic ; Graft vs Host Disease ; genetics ; immunology ; pathology ; Hematopoietic Stem Cell Transplantation ; Human Umbilical Vein Endothelial Cells ; cytology ; drug effects ; immunology ; Humans ; Leukemia, Myeloid ; genetics ; immunology ; pathology ; therapy ; Lymphoma, Non-Hodgkin ; genetics ; immunology ; pathology ; therapy ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; immunology ; pathology ; therapy ; Retrospective Studies ; Signal Transduction ; Transplantation, Homologous ; Tumor Necrosis Factor-alpha ; pharmacology ; Vascular Endothelial Growth Factor A ; genetics ; immunology

No abstract available.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cyclophosphamide/therapeutic use ; Doxorubicin/therapeutic use ; Female ; Humans ; Immunoglobulin Variable Region/genetics ; Leukemia, Hairy Cell/drug therapy/*genetics/pathology ; Lymphoma, Non-Hodgkin/drug therapy/*genetics/pathology ; MAP Kinase Kinase 1/*genetics ; Male ; Middle Aged ; Mutation ; Polymorphism, Single Nucleotide ; Prednisone/therapeutic use ; Pregnancy ; Proto-Oncogene Proteins B-raf/*genetics ; Real-Time Polymerase Chain Reaction ; Vincristine/therapeutic use