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1.
Article in Chinese | WPRIM | ID: wpr-880144

ABSTRACT

OBJECTIVE@#To investigate the relationship between the polymorphism of miR-155 and its target gene MyD88 and clinicopathological features of diffuse large B-cell lymphoma (DLBCL).@*METHODS@#135 cases of DLBCL patients in our hospital from March 2015 to August 2017 were selected, and 90 cases of reactive hyperplasia of lymph nodes were selected as the control group. The relative expression of miR-155 and MyD88 gene polymorphism were detected in the two groups, and the relationship between miR-155 and MyD88 gene polymorphism and clinicopathological characteristics of DLBCL was analyzed.@*RESULTS@#The relative expression of miR-155 in DLBCL patients was significantly higher than that in the control group (P<0.05). The mutation rate of MyD88 L265P in DLBCL group was significantly higher than that in control group (P<0.05). The relative expression of miR-155 in patients with MyD88 L265P mutation was significantly higher than that in patients with wild-type DLBCL (P<0.05). The relative expression of miR-155 and the polymorphism of MyD88 L265P were associated with lesion location, stage, BCL-2 protein expression and MyD88 protein expression in DLBCL patients (t=7.461、8.804、6.487、10.812; χ@*CONCLUSION@#The abnormal expression of miR-155 and the mutation rate of MyD88 gene in DLBCL patients are increased, and the expression of miR-155 and the mutation of MyD88 gene affect the disease progression and prognosis of patients, which may be potential biological indicators for the diagnosis, treatment and prognosis of DLBCL.


Subject(s)
Humans , Lymphoma, Large B-Cell, Diffuse/genetics , MicroRNAs/genetics , Mutation , Myeloid Differentiation Factor 88/genetics , Polymorphism, Genetic , Prognosis
2.
Article in Chinese | WPRIM | ID: wpr-880126

ABSTRACT

Diffuse large B-cell lymphoma (DLBCL) as an aggressive lymphoma, there has not a good molecular marker to assess the therapeutic efficacy and prognosis of the disease. As compared with the traditional deteation method, it was found that the circulating tumor DNA (ctDNA) can be used as a non-invasive specific biomarker which can dynamically provide the information about the lymphoma. ctDNA in DLBCL can be obtained by dideoxy chain termination method combined with PCR, so as to detect genetic markers, targeted sequences of gene which is related to lymphoma; the digital PCR (dPCR) for lymphoma somatic mutations and the detection of abnormal methylation; ctDNA is closely related to the diagncsis, therapeutic efficiency and prognosis of DLBCL, thus ctDNA can be used for the early detection, mid-term and prognostic monitoring in DLBCL, which makes ctDNA have a broad clinical applied prospect.


Subject(s)
Biomarkers, Tumor , Circulating Tumor DNA , Humans , Lymphoma, Large B-Cell, Diffuse/genetics , Polymerase Chain Reaction , Prognosis
3.
Chinese Medical Journal ; (24): 253-260, 2020.
Article in English | WPRIM | ID: wpr-877995

ABSTRACT

Although the first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone regimen (R-CHOP) substantially improved outcomes for patients with diffuse large B-cell lymphoma (DLBCL), 40% of the patients suffered from relapsed/refractory disease and had poor survival outcomes. The detailed mechanism underlying R-CHOP resistance has not been well defined. For this review, we conducted a thorough search for literature and clinical trials involving DLBCL resistance. We discussed DLBCL biology, epigenetics, and aberrant signaling of the B-cell receptor (BCR), phosphatidylinositol 3-kinase (PI3K)/Akt, nuclear factor kappa light chain enhancer of activated B-cells (NF-κB), and the Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathways as defining mechanisms of DLBCL heterogeneity and R-CHOP resistance. The cell of origin, double- or triple-hit lymphoma and double-protein-expression, clonal evolution, tumor microenvironment, and multi-drug resistance help to contextualize DLBCL resistance in an (epi)genetically and biologically comparative manner. With better understanding of the biological and molecular landscape of DLBCL, a more detailed classification system and tailored treatments will ideally become available to further improve the prognosis of DLBCL patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Humans , Lymphoma, Large B-Cell, Diffuse/genetics , Phosphatidylinositol 3-Kinases , Prednisone/therapeutic use , Prognosis , Rituximab/therapeutic use , Tumor Microenvironment , Vincristine/therapeutic use
4.
Rev. méd. Chile ; 147(2): 247-250, Feb. 2019.
Article in Spanish | LILACS | ID: biblio-1004339

ABSTRACT

Patients transplanted from solid organs have an increased risk of cancer, especially lymphomas. Lymphomas correspond to 4 to 5% of malignant neoplasms in the general population and in solid organ transplant patients it reaches an incidence of 21%. The incidence of non-Hodgkin lymphomas is 10 times higher than in the non-transplanted population. We report the case of a 68-year-old man with a kidney transplant who 6 years after transplantation, developed a non-Hodgkin diffuse large cells B lymphoma with lymph node and pulmonary involvement, with markers of very poor prognosis (triple MYC expressor, BCL2 and BCL6). and its evolution with chemotherapy with DA R EPOCH.


Subject(s)
Humans , Male , Aged , Lymphoma, Non-Hodgkin , Lymphoma, Large B-Cell, Diffuse/genetics , Vincristine/therapeutic use , Lymphoma, Non-Hodgkin/etiology , Lymphoma, Non-Hodgkin/drug therapy , Prednisone/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Doxorubicin/therapeutic use , Biomarkers, Tumor/genetics , Genes, myc/genetics , Lymphoma, Large B-Cell, Diffuse/etiology , Lymphoma, Large B-Cell, Diffuse/drug therapy , Kidney Transplantation/adverse effects , Proto-Oncogene Proteins c-bcl-2/genetics , Cyclophosphamide/therapeutic use , Proto-Oncogene Proteins c-bcl-6/genetics , Etoposide/therapeutic use
5.
Rev. méd. Chile ; 145(11): 1485-1489, nov. 2017. graf
Article in Spanish | LILACS | ID: biblio-902470

ABSTRACT

High-grade B-cell lymphomas with rearrangement of MYC, BCL-2 and/or BCL-6 were introduced by the update of the WHO classification of lymphoid neoplasms. They usually present unique morphological and molecular characteristics, with an aggressive clinical outcome and worse prognosis. We report a 48 year-old female patient presenting with B symptoms and enlarged lymph nodes. Blood count showed pancytopenia and peripheral blood smears showed large lymphoid cells, some with nuclei and vacuoles. LDH was 3524 g/L and serum calcium was 11.5 mg/dL. Flow cytometry immunophenotyping showed pathological mature B lymphocytes. Protein electrophoresis showed a slight monoclonal peak. The biopsy disclosed a triple expressor diffuse large B-cell lymphoma, arising from germinal center. FISH was positive for MYC, BCL-2 and BCL-6 (triple hit) with a clonal evolution. Conventional cytogenetics showed a complex karyotype. Chemotherapy was started with R-CHOP (Rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone). She developed impaired consciousness; the brain CT scan showed a large brain mass. The patient died within 3 weeks.


Subject(s)
Humans , Female , Middle Aged , Translocation, Genetic/genetics , Lymphoma, Large B-Cell, Diffuse/genetics , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-6/genetics , Hypercalcemia/etiology , Tomography, X-Ray Computed , Lymphoma, Large B-Cell, Diffuse/complications , Lymphoma, Large B-Cell, Diffuse/pathology , Fatal Outcome , Karyotype
6.
Egyptian Journal of Medical Human Genetics [The]. 2014; 15 (1): 7-13
in English | IMEMR | ID: emr-154342

ABSTRACT

Given the importance of understanding the genetic variations involved in the pathogenesis of non-Hodgkin's lymphoma [NHL], this work was designed to study the impact of IL-10 [-1082 G/A; rs!800896 and -819 C/T; rs!800871] gene promoter polymorphism on susceptibility of Egyptians to diffuse large B cell lymphoma [DLBCL]; the major type of NHL. To the best of our knowledge, this study is the first one that examines IL-10 promoter polymorphism in DLBCL in Egyptians. Genotyping polymorphism is performed using sequence-specific primers polymerase chain reaction [SSP-PCR] in 100 Egyptian DLBCL patients and 119 normal controls. Circulating plasma levels of IL-10 were measured using Enzyme-linked immunosorbent assay [ELISA]. Insignificant change in IL-10 [-1082 and -819] genotypes was recorded. Although A allele is slightly decreased in DLBCL patients, it did not reach statistical significance. GT haplotype was significantly elevated [P < 0.05] in NHL patients. A significant linkage disequilibrium between the -1082 and 819 SNPs with D' = 0.596 and r[2] = 0.1032 [P < 0.001] was demonstrated. Significantly increased plasma IL-10 [P < 0.01] was found which is positively correlated [r = 0.307; P < 0.01] with the disease Taken together, our findings demonstrated that IL-10 promoter gene polymorphism [-1082 and -819] may not have an influence on the clinical outcome of DLBCL, especially in terms of overall secretion level. Further investigations of other cytokine gene polymorphisms will lead to a better understanding of the disease's biological background


Subject(s)
Humans , Male , Female , Lymphoma, Large B-Cell, Diffuse/genetics , Polymorphism, Genetic , Enzyme-Linked Immunosorbent Assay/methods , Genotype , Interleukin-10/blood
8.
Säo Paulo med. j ; 128(1): 14-17, Jan. 2010. tab
Article in English | LILACS | ID: lil-547398

ABSTRACT

CONTEXT AND OBJECTIVE: Gene expression and immunohistochemical profiling of diffuse large B-cell lymphoma (DLBCL) have revealed important prognostic subgroups: germinal center B-cell-like (GCB-like) DLBCL and activated B cell-like (ABC-like) DLBCL. Although few reports on high-risk DLBCL are available, the prognosis for the GCB-like subgroup has been shown to be better than that of the ABC-like subgroup. The role of Bcl-2 as a predictor of survival in DLBCL cases is unclear and its expression varies between the two subgroups of DLBCL. In this study, we analyzed the frequency and prognostic impact of Bcl-2 protein expression in high-risk DLBCL cases. DESIGN AND SETTING: Retrospective cohort study among DLBCL patients treated at Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP). METHODS: The prognostic impact of the expression of the proteins CD10, Bcl-6, MUM1 (multiple myeloma oncogene-1) and Bcl-2 on high-risk DLBCL cases was evaluated by means of immunohistochemistry. Seventy-three patients aged 18-60 years were evaluated for all these markers. RESULTS: Twenty-four cases (32.9 percent) were GCB-like and 49 (67.1 percent) were ABC-like, with no difference regarding complete remission, disease-free survival or overall survival rates. Twenty-seven patients (37 percent) showed Bcl-2 expression, which was the only independent factor predicting a worse prognosis for overall survival according to multivariate analysis. CONCLUSION: Bcl-2 protein was expressed in 37 percent of the high-risk DLBCL patients, without any difference between the ABC-like DLBCL and GCB-like DLBCL cases.


CONTEXTO E OBJETIVO: A expressão gênica e imunoistoquímica do linfoma difuso de grandes células B (LDGCB) vem permitindo a identificação de importantes subgrupos prognósticos: LDGCB do centro germinativo (CG) e LDGCB de células B ativadas (CBA). Entretanto, existem poucos dados disponíveis com LDGCB de alto risco, sendo o prognóstico dos LDGCB do CG melhor que os LDGCB de CBA. A participação do Bcl-2 como preditor de sobrevida nos LDGCB não é clara e sua expressão é variável entre os dois subgrupos de LDGCB. Neste estudo é avaliada a frequência e o prognóstico da expressão da proteína Bcl-2 em LDGCB de alto risco. TIPO DE ESTUDO E LOCAL: Estudo de coorte retrospectivo realizado entre portadores de LDGCB tratados no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. MÉTODOS: Foi avaliado o impacto prognóstico da expressão das proteínas CD10, Bcl-6, MUM1 (multiple myeloma oncogene-1) e Bcl-2 por imunoistoquímica em LDGCB de alto risco. Foram avaliados, para todos os marcadores, 73 pacientes com idade de 18 a 60 anos. RESULTADOS: Vinte e quatro (32,9 por cento) pacientes foram classificados como LDGCB do CG e 49 (67,1 por cento) como LDGCB de CBA, sem diferença nas taxas de remissão completa, sobrevida livre de doença e sobrevida global. Vinte e sete (37 por cento) apresentaram expressão de Bcl-2, o qual foi o único fator preditivo independente de pior prognóstico de sobrevida global à análise multivariada. CONCLUSÃO: A expressão da proteína Bcl-2 ocorreu em 37 por cento dos portadores de LDGCB de alto risco, sem diferença entre os subgrupos de LDGCB do CG ou de CBA.


Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Lymphoma, Large B-Cell, Diffuse/metabolism , /metabolism , Biomarkers, Tumor/metabolism , Chi-Square Distribution , Cohort Studies , Disease-Free Survival , DNA-Binding Proteins/metabolism , Gene Expression , Germinal Center/metabolism , Immunohistochemistry , Lymphoma, Large B-Cell, Diffuse/genetics , Myeloma Proteins/metabolism , Neprilysin/metabolism , Prognosis , Retrospective Studies , Young Adult
9.
Article in Korean | WPRIM | ID: wpr-70820

ABSTRACT

Aanaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (DLBCL) is an unusual disease entity first reported in 1997 as DLBCL with expression of full-length ALK protein. The World Health Organization classification enlists the disease as a rare variant of DLBCL. Herein we describe two cases of ALK-positive DLBCL with cytomorphologic and molecular characteristics for the first time in Korea. The patients were 35-yr-old and 24-yr-old male patients. Immunohistochemical studies on the lymph nodes revealed large sized neoplastic cells with plasmablastic differentiation, which were negative for CD30 and positive for ALK with the characteristic granular staining in the cytoplasmic region. Extensive involvement of bone marrow was observed in both cases showing large, extremely atypical cells. Fluorescence in situ hybridization and molecular studies on the bone marrow aspirate specimens led to the detection of a clathrin (CLTC)/ALK rearrangement. Despite aggressive chemotherapy, the patients died 15 and 17 months after the diagnosis, indicating poor prognosis of the disease entity. This is the first report demonstrating the cytomorphologic findings of ALK-positive DLBCL cells on bone marrow aspirates.


Subject(s)
Adult , Bone Marrow/pathology , Clathrin/genetics , Fatal Outcome , Gene Fusion , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Lymphoma, Large B-Cell, Diffuse/genetics , Male , Protein-Tyrosine Kinases/genetics , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNA
10.
Article in English | WPRIM | ID: wpr-191667

ABSTRACT

The metastasis-suppressing role of the nm23 gene in the metastatic spread of malignant tumor is still debated. We examined the nm23-H1 protein expression and gene mutation in non-Hodgkin's lymphomas to compare with the clinicopathologic parameters. The expression of nm23-H1 protein was immunohistochemically examined in 150 cases of non-Hodgkin's lymphomas; 85 diffuse large B cell lymphomas (DL-BCL), 18 marginal zone B cell lymphomas (MZL), 3 mantle cell lymphomas, 25 peripheral T cell lymphomas, not otherwise specified (TCLNOS), and 19 NK/T cell lymphomas (NK/T). Eighty-one cases (58 DLBCL, 6 MZL, 4 TCLNOS, and 13 NK/T) were studied for nm23-H1 gene mutation in exon 1 to 5. The high expression of nm23-H1 protein was associated with the high IPI score (p=0.019) and the low survival rate of the patients (p=0.0039). The gene mutation of nm23-H1 was detected in 10.3% of DLBCL and 30.7% of NK/T; but none in MZL and TCLNOS. The mutation was found in exon 1 in 5 cases, exon 2 in two cases, exon 4 in one case and both exon 1 and 2 in two cases. Our results suggest that the expression of nm23-H1 protein can be used as a poor prognostic marker in non-Hodgkin's lymphomas, and the mutational change of gene may operate in the lymphomagenesis.


Subject(s)
Tissue Array Analysis , Survival Analysis , Prognosis , Polymorphism, Single-Stranded Conformational , Nucleoside-Diphosphate Kinase/genetics , Mutation/genetics , Middle Aged , Male , Lymphoma, T-Cell/genetics , Lymphoma, Non-Hodgkin/genetics , Lymphoma, Mantle-Cell/genetics , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, B-Cell/genetics , Immunohistochemistry , Humans , Female , DNA Mutational Analysis , Base Sequence
11.
Saudi Medical Journal. 2005; 26 (2): 251-5
in English | IMEMR | ID: emr-74804

ABSTRACT

Follicular lymphoma [FL], a common subtype of non-Hodgkin's lymphoma [NHL] in the West, represents a rare subtype in Jordan. Bcl-2 gene rearrangement plays a crucial role in the biology of the vast majority of FL and a substantial number of diffuse large B-cell lymphoma [DLBCL] in the West; but its presence has not been studied in Jordan. Our aims are to document if bcl-2 gene rearrangement exists in Jordanian FL and DLBCL, and if present to determine whether its frequency among these lymphomas is different from the West and therefore may be responsible for some of the epidemiological differences seen between Jordan and the West. The study was conducted in the year 2001 using polymerase chain reaction [PCR], to detect bcl-2 gene rearrangement in paraffin sections in 5 FL and 23 DLBCL cases diagnosed at the Department of Pathology at Jordan University of Science and Technology, Irbid, Jordan. Two sets of primers including the major breakpoint region [MBR] and the minor cluster region [MCR] were used. Amplifiable DNA was extracted from all cases. Bcl-2 gene rearrangement was seen among 4 [80%] of 5 FL cases, and 8 [35%] of 23 DLBCL cases. The majority of the rearrangements involved the MBR; however, one fourth of cases [one of 4 FL; 2 of 8 DLBCL] with bcl-2 rearrangement involved the MCR. Bcl-2 gene rearrangement was seen in the vast majority of Jordanian FL cases and approximately one third of all DLBCL cases. These figures are similar to those reported in the West, and therefore bcl-2 gene rearrangement does not help in explaining the epidemiological differences of NHL between Jordan and the West. The presence of bcl-2 gene rearrangement in DLBCL may define a subset of lymphomas that may be biologically and clinically unique and different from the rest of DLBCL


Subject(s)
Humans , Male , Female , Lymphoma, Large B-Cell, Diffuse/genetics , Gene Rearrangement, B-Lymphocyte , Polymerase Chain Reaction , Genes, bcl-2/genetics , DNA, Neoplasm/genetics , Seroepidemiologic Studies
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