OBJECTIVE: To investigate the effect of TBL1XR1 mutation on cell biological characteristics of diffuse large B-cell lymphoma (DLBCL). METHODS: The TBL1XR1 overexpression vector was constructed and DNA sequencing was performed to determine the mutation status. The effect of TBL1XR1 mutation on apoptosis of DLBCL cell line was detected by flow cytometry and TUNEL fluorescence assay; CCK-8 assay was used to detect the effect of TBL1XR1 mutation on cell proliferation; Transwell assay was used to detect the effect of TBL1XR1 mutation on cell migration and invasion; Western blot was used to detect the effect of TBL1XR1 mutation on the expression level of epithelial-mesenchymal transition (EMT) related proteins. RESULTS: The TBL1XR1 overexpression plasmid was successfully constructed. The in vitro experimental results showed that TBL1XR1 mutation had no significant effect on apoptosis of DLBCL cells. Compared with the control group, TBL1XR1 mutation enhanced cell proliferation, migration and invasion of DLBCL cells. TBL1XR1 gene mutation significantly increased the expression of N-cadherin protein, while the expression of E-cadherin protein decreased. CONCLUSION TBL1XR1 mutation plays a role in promoting tumor cell proliferation, migration and invasion in DLBCL. TBL1XR1 could be considered as a potential target for DLBCL therapy in future research.
Humans ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Cell Proliferation ; Mutation ; Receptors, Cytoplasmic and Nuclear/genetics* ; Apoptosis ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition ; Cell Movement ; Repressor Proteins/genetics* ; Nuclear Proteins/genetics* ; Cadherins/metabolism*

<b>OBJECTIVEb>To study the clinicopathologic features and significance of aberrant CD56 expression in diffuse large B-cell lymphoma (DLBCL).

<b>METHODSb>The clinical and pathologic profiles of 10 cases of DLBCL with aberrant expression of CD56 were investigated. Immunohistochemical staining, in-situ hybridization for Epstein-Barr virus encoded RNA and gene rearrangement for IgH and Igκ were carried out.

<b>RESULTSb>There were 6 male and 4 female patients. The medium age of patients was 46 years. All of them presented with extranodal lymphoma involvement, with gastrointestinal tract being the commonest site (5/10). Histologic examination showed that most of the atypical lymphoid cells were centroblast-like and demonstrated a diffuse growth pattern. Apoptosis and necrosis were identified in some cases. Immunohistochemical study showed that the tumor cells were positive for CD20 or CD79α and aberrantly expressed CD56. Five cases had the GCB phenotype while the remaining cases had the non-GCB phenotype, according to Hans classification. Bcl-6 was positive in most cases (9/10). All cases showed a high proliferation index by Ki-67. The tumor cells were negative for CD3ε, CD138 and granzyme B. In-situ hybridization for Epstein-Barr virus encoded RNA was performed in 7 cases and none of them showed positive signals. IgH gene rearranged bands were detected in 4 cases (4/6) and Igκ was detected in 3 cases (3/6). Follow-up data were available in 8 patients. Two patients died of disease progression within 5 to 13 months after diagnosis and the other 6 patients were alive 8 to 60 months after therapy.

<b>CONCLUSIONSb>DLBCL with aberrant expression of CD56 is rare. Most of them present with extranodal involvement, show high frequency of bcl-6 expression and high proliferation index. The patients often have good response to chemotherapy.

Antigens, CD20 ; metabolism ; Apoptosis ; CD56 Antigen ; metabolism ; CD79 Antigens ; metabolism ; Disease Progression ; Female ; Gene Rearrangement ; Granzymes ; metabolism ; Herpesvirus 4, Human ; genetics ; Humans ; Immunophenotyping ; In Situ Hybridization ; Lymphoma, Large B-Cell, Diffuse ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; Necrosis ; Phenotype ; Proto-Oncogene Proteins c-bcl-6 ; metabolism ; RNA, Viral ; analysis

<b>OBJECTIVEb>To study the clinicopathologic features, immunophenotype and gene rearrangement of primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL).

<b>METHODSb>Seven cases of PCLBCL were enrolled into the study. Clinicopathologic analysis, immunohistochemical staining and gene rearrangement for IgH and Igκ were undertaken in the study.

<b>RESULTSb>All the seven cases were male, and the median age was 72 years. Patients usually presented with multiple purple tumors, nodules, papules and infiltrative plaques. Two patients had a history of leg injury before onset, and one had mosquito bites. Histologically, the tumor involved the dermis and subcutis with dense and diffuse infiltrative pattern composing of centroblasts and/or immunoblasts. Immunohistochemical staining showed that seven cases (7/7) expressed CD20, six (6/6) expressed bcl-2, four (4/4) expressed MUM-1, four (4/5) expressed CD79a, four (4/5) expressed PAX-5 and four (4/6) expressed bcl-6, respectively. All cases did not express CD3ε, CD45RO, CD10 and CD30. IgH gene rearranged bands were detected in three (3/6) cases and Igκ was detected in one (1/5) case. Six of the seven cases died and the remaining patient, who was 44-year-old, was alive after 22 months of follow-up.

<b>CONCLUSIONSb>PCLBCL is rare, predominantly affects elderly male patients. PCLBCL has poor prognosis and high mortality, but younger patients seem to have better prognosis. Some cases had a history of trauma or mosquito bites. The relationship between the history and the onset of PCLBCL needs further evaluation.

Aged ; Aged, 80 and over ; Animals ; Antigens, CD ; analysis ; Culicidae ; Gene Rearrangement ; Humans ; Immunoglobulin Heavy Chains ; genetics ; Immunoglobulin kappa-Chains ; genetics ; Immunophenotyping ; Insect Bites and Stings ; complications ; Leg ; Leg Injuries ; complications ; Lymphoma, Large B-Cell, Diffuse ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; Prognosis ; Proto-Oncogene Proteins c-bcl-6 ; metabolism ; Skin Neoplasms ; genetics ; pathology

<b>OBJECTIVEb>we aimed to investigate the mutation and expression of BRAF gene in mature T/NK cell lymphoma tissues and cell lines, explore the correlation between gene alterations and clinicopathological features and clinical outcomes of mature T/NK cell lymphoma.

<b>METHODSb>Firstly, we detected common mutant sites of BRAF (locus 1 799 mutation in exon 15 and loci 463, 465 and 468 mutation in exon 11) in lymphoma Jurkat, Hut-78 and YTS cell lines, normal peripheral blood lymphocytes, different types of mature T/NK cell lymphoma and reactive hyperplasia lymph nodes by direct sequencing. Then we measured the expression of BRAF in Jurkat, Hut-78, YTS cells and normal peripheral blood lymphocytes by real time-PCR and Western-blot detection. We also used immunohistochemistry (IHC) to detect the expression of BRAF in mature T/NK cell lymphoma tissues and reactive hyperplasia lymph nodes, and to analyze the correlation between the expression of BRAF and clinocopathological features and clinical outcomes.

<b>RESULTSb>We did not find common BRAF mutation in mature T/NK cell lymphoma tissues and cell lines, and the relatively expression of BRAF gene mRNA in normal peripheral blood lymphocytes, YTS, Hut-78 and Jurkat cells were 1.000, 5.207±0.013, 8.412±0.615 and 36.720±1.797, respectively, and protein expressions were 0.051±0.003, 0.102±0.013, 0.113±0.017 and 0.304±0.010, respectively, and the expression of BRAF in peripheral T cell lymphoma Jurkat cells was significantly higher than that of Hut-78, YTS cells and normal lymphocytes (P<0.05). Only 6 of 58 peripheral T cell lymphomas (10.3%) had positive BRAF expression, and were the subgroups of peripheral T cell lymphoma-unspecified type. The statistical data did not show any correlation between positive expression of BRAF and gender, age, clinical stage, location, lactate dehydrogenase in the 21 cases of peripheral T cell lymphoma-unspecified type (P<0.05), but the positive rate of BRAF in the effective treatment group (8.3%) was significantly lower than that of the invalid group (55.6%, P<0.05).

<b>CONCLUSIONb>The expression of BRAF gene may become a marker of malignant biological characteristics and clinical therapeutic target of peripheral T cell lymphoma.

Exons ; Humans ; Immunohistochemistry ; Killer Cells, Natural ; Lymphoma, T-Cell, Peripheral ; genetics ; metabolism ; pathology ; Proto-Oncogene Proteins B-raf ; genetics ; metabolism ; Pseudolymphoma ; genetics ; metabolism ; RNA, Messenger ; metabolism

No abstract available.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Burkitt Lymphoma/*pathology ; Child, Preschool ; Cyclophosphamide/therapeutic use ; Doxorubicin/therapeutic use ; Female ; Gene Rearrangement ; Herpesvirus 4, Human/metabolism ; Humans ; Immunohistochemistry ; Lymphoma, B-Cell/*diagnosis/drug therapy ; Lymphoma, Large B-Cell, Diffuse/*pathology ; Male ; Prednisone/therapeutic use ; Proto-Oncogene Proteins c-myc/genetics ; Tomography, X-Ray Computed ; Vincristine/therapeutic use ; Viral Matrix Proteins/immunology/metabolism

No abstract available.
Antibodies, Monoclonal, Murine-Derived/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; B-Cell-Specific Activator Protein/metabolism ; Bone Marrow/metabolism/*pathology ; Cyclophosphamide/therapeutic use ; Doxorubicin/therapeutic use ; Endoscopy, Digestive System ; Female ; Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor ; Genetic Loci ; Humans ; Liver/metabolism/pathology ; Lymphocytes/cytology/immunology ; Lymphoma, Large B-Cell, Diffuse/complications/*diagnosis/drug therapy ; Lymphoma, T-Cell, Peripheral/complications/*diagnosis/drug therapy ; Middle Aged ; Prednisone/therapeutic use ; Receptors, Antigen, T-Cell, gamma-delta/genetics ; Tomography, X-Ray Computed ; Vincristine/therapeutic use

<b>OBJECTIVEb>To study the histological features, diagnosis, differential diagnoses of aggressive B-cell lymphomas of the gastrointestinal tract and to correlate clinical prognosis with pathologic parameters and immunophenotypes with an emphasis on c-myc, Tcl-1 and CD38 expression and their values in predicting the status of c-myc gene translocation.

<b>METHODSb>Fifty-four cases of aggressive B-cell lymphomas of the gastrointestinal tract with complete clinical and pathologic data were retrospectively collected. The clinical data, histologic and immunohistochemical findings and follow-up results were analyzed. Predictive immunohistochemical stains including c-myc, Tcl-1 and CD38 were performed and ROC curve analysis was used to confirm the accuracy of these markers in predicting c-myc translocation.

<b>RESULTSb>Of 54 cases, there were 33 males and 21 females with median age of 56 years. Histological types of lymphomas included 49 cases of DLBCL (11 cases of germinal central B cell like and 38 cases of activated B cell like by Hans classification), 4 cases of DLBCL/BL and 1 case of BL. Eleven of 54 patients died within 97 months, with median survival of 42 months. Histologically, full-thickness infiltration of the gastrointestinal tract by large atypical cells with evident phagocytosis of karyorrhexis by macrophages ("starry sky") were seen in 18/54 cases. The lymphoma cells were positive for CD20 (54/54), CD79a (54/54), CD43 (4/54), CD5 (7/54), bcl-2 (26/54), Tcl-1 (17/54) and CD38 (15/54), but all negative for CD3 and CD30. The proliferative index by Ki-67 ranged from 40% to 100%. The univariate survival analysis indicated that B symptoms, general performance, high LDH, high IPI, distant metastasis, high clinical stage and tumors with over 90% of cells positive for c-myc were negative predictors for the patient's survival. In addition, cases of DLBCL positive for CD5 had an unfavorable prognosis. Cox regression analysis showed c-myc translocation, distant metastasis and high LDH were independent predictors for unfavorable prognosis. ROC curve revealed the percentage of c-myc positivity predicted the presence of c-myc gene translocation, with 75% as the optimal threshold.

<b>CONCLUSIONSb>Aggressive B-cell lymphomas of the gastrointestinal tract with a prognosis influenced by variable clinicopathologic factors. DLBCL and DLBCL/BL may possess c-myc translocation and tend to be Burkitt-like or atypical Burkitt lymphoma. As independent prognostic indicator, c-myc expression may be used for selection of therapeutic regimens and prognostication. High percentage of tumor cells with c-myc positivity may be used to predict the presence of c-myc gene translocation.

ADP-ribosyl Cyclase 1 ; metabolism ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Burkitt Lymphoma ; genetics ; pathology ; therapy ; Child ; Female ; Follow-Up Studies ; Humans ; Intestinal Neoplasms ; genetics ; pathology ; therapy ; Lymphoma, Large B-Cell, Diffuse ; genetics ; pathology ; therapy ; Male ; Middle Aged ; Prognosis ; Proto-Oncogene Proteins ; metabolism ; Proto-Oncogene Proteins c-myc ; genetics ; metabolism ; ROC Curve ; Retrospective Studies ; Stomach Neoplasms ; genetics ; pathology ; therapy ; Translocation, Genetic ; Young Adult

Ataxia telangiectasia mutated (ATM) kinase plays an essential role in the maintenance of genomic stability. ATM-deficient (ATM(-/-)) mice exhibit hematopoietic stem cell (HSC) dysfunction and a high incidence of lymphoma. Gadd45a controls cell cycle arrest, apoptosis and DNA repair, and is involved in the ATM-p53 mediated DNA damage response. However, the role of Gadd45a in regulating the functionality of ATM(-/-) HSCs is unknown. Here we report that Gadd45a deletion did not rescue the defects of T-cells and B-cells development in ATM(-/-) mice. Instead, ATM and Gadd45a double knockout (ATM(-/-) Gadd45a(-/-)) HSCs exhibited an aggravated defect in long-term self-renewal capacity compared to ATM(-/-) HSCs in HSC transplantation experiments. Further experiments revealed that the aggravated defect of ATM(-/-) Gadd45a(-/-) HSCs was due to a reduction of cell proliferation, associated with an accumulation of DNA damage and subsequent activation of DNA damage response including an up-regulation of p53-p21 signaling pathway. Additionally, ATM(-/-) Gadd45a(-/-) mice showed an increased incidence of hematopoietic malignancies, as well as an increased rate of metastasis than ATM(-/-) mice. In conclusion, Gadd45a deletion aggravated the DNA damage accumulation, which subsequently resulted in a further impaired self-renewal capacity and an increased malignant transformation in ATM(-/-) HSCs.
Animals ; Ataxia Telangiectasia Mutated Proteins ; genetics ; B-Lymphocytes ; pathology ; Cell Cycle Proteins ; genetics ; Cell Proliferation ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; DNA Damage ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; metabolism ; pathology ; Leukemia ; genetics ; pathology ; Lymphoma ; genetics ; pathology ; Mice, Knockout ; Neoplasm Metastasis ; Nuclear Proteins ; genetics ; T-Lymphocytes ; pathology ; Tumor Suppressor Protein p53 ; metabolism

Animals ; Gene Amplification ; Genes, myc ; Humans ; Lymphoma, B-Cell ; genetics ; metabolism ; pathology ; Mutagenesis, Insertional ; Proto-Oncogene Proteins c-myc ; metabolism ; Translocation, Genetic

<b>OBJECTIVEb>To study the relationship between myc gene rearrangement and myc protein expression in diffuse large B cell lymphoma (DLBCL), and their correlation with prognosis.

<b>METHODSb>One hundred and six cases of DLBCLs with follow-up data were analyzed using interphase fluorescence in situ hybridization (FISH) technique. Immunophenotyping analysis for CD20, CD3, myc, Mum-1, CD10, bcl-6 was also performed using EnVision immunohistochemistry.

<b>RESULTSb>The percentages of tumor cells expressing myc, Mum-1, CD10 and bcl-6 were 70.8%, 56.6%, 21.7% and 26.4%, respectively. Twenty six cases (24.5%) were of GCB type and the rest (75.5%) were of non-GCB (non germinal center) type. The myc rearrangement was identified in 13 (12.3%) of 106 cases. 13 cases showed to be of non-GCB type. There was no correlation between myc rearrangement and myc protein expression. DLBCLs (n = 13) with myc rearrangement showed significantly poorer overall survival (OS) and progression free survival (PFS), with a median OS and PFS time of 4.7 and 3.2 months, respectively (for OS and PFS, P < 0.001). Multivariate analysis using Cox proportional hazard model confirmed that myc rearrangement, ECOG performance status of 2-4, immunophenotyping subgroup and myc protein were independent factors affecting the prognosis and significantly associated with the survival. However, myc rearrangement was the strongest prognostic factor.

<b>CONCLUSIONSb>DLBCL with myc gene rearrangement is a subgroup of non-GCB DLBCL with poor outcome. It is an independent and useful factor for prognosis in DLBCL. Expression of myc is influenced by many factors and myc rearrangement may be one of these factors.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cyclophosphamide ; therapeutic use ; Disease-Free Survival ; Doxorubicin ; therapeutic use ; Female ; Follow-Up Studies ; Gene Rearrangement, B-Lymphocyte ; Genes, myc ; Humans ; In Situ Hybridization, Fluorescence ; Interferon Regulatory Factors ; metabolism ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Neprilysin ; metabolism ; Prednisone ; therapeutic use ; Proportional Hazards Models ; Proto-Oncogene Proteins c-bcl-6 ; metabolism ; Proto-Oncogene Proteins c-myc ; metabolism ; Survival Rate ; Vincristine ; therapeutic use