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Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The WHO classification of malignant lymphoma presents a list of disease entities well defined by clinical, immunologic and genetic features. The disease entities are primarily exemplified by mantle cell lymphoma (the relative incidence, 3%, related with an aberrant expression of cyclin D1 activated by t(11;14) chromosomal translocation), follicular lymphoma (7%, with BCL2 by t(14;18) translocation), marginal zone B-cell lymphoma of MALT type (8%, with MALT1 by t(11;18) or t(14;18) translocation), adult T-cell leukemia/lymphoma (7%, but 20% in Kyushu, with human T-cell leukemia virus type 1 [HTLV1]), extranodal NK/T-cell lymphoma of nasal type (2%, with Epstein-Barr virus [EBV]), and anaplastic large cell lymphoma (2%, with ALK by t(2;5) translocation). The genetic alterations or agents related with their pathogenesis are of great relevance to the diagnoses of these entities. Conversely, the category of diffuse large B-cell lymphoma occupies the largest percentage (33%), and is heterogeneous, including several subtypes. The diagnoses of lymphoma subtypes, except for the main entities described above, largely depends on the phenotypic analysis, in addition to their clinical manifestations and histologic evaluations. Therefore, much attention should be paid to the diagnostic pitfalls in the phenotypic analysis of T-cell lymphomas in regard to incorrect classification of lymphoma, due to lack of awareness or incomplete immunophenotypic evaluation; incorrect interpretation of immunophenotypic data, due to failure to correlate them with the other laboratory data; and suboptimal quality of immunohistochemical stains, leading to a wrong conclusion.
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PMID:[World Health Organization (WHO) classification of malignant lymphoma--how is the WHO now?]. 1499 43

The purpose of this study was to investigate the prognostic effects of four biological markers, BCL2, TP53, Ki-67, and P-glycoprotein, and their possible clinical relevance in addition to the international prognostic index (IPI) in diffuse large B-cell lymphoma (DLBCL). A total of 405 patients with aggressive lymphoma, stage II-IV, between 18 and 67 years, were randomized in a trial comparing CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin). Of these, 267 cases were classified as DLBCL, with adequate paraffin blocks available in 207 cases, enabling immunohistochemical assessment of the expression of BCL2, TP53, P-glycoprotein, and Ki-67. In a multivariate analysis, stratified for IPI, high BCL2 expression (>10%) low (<60%) expression of Ki-67, and high TP53 protein expression (>75%) were shown to provide additional prognostic information with regard to overall or failure-free survival. We found no association between expression of P-glycoprotein and outcome. Assessment of BCL2 positivity might be introduced as part of the routine investigation in patients with DLBCL, but further studies are necessary to confirm the clinical relevance of Ki-67 and TP53 expression.
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PMID:Assessment of biological prognostic factors provides clinically relevant information in patients with diffuse large B-cell lymphoma--a Nordic Lymphoma Group study. 1508 85

Previously, we have shown that patients with diffuse large B-cell lymphoma (DLBCL) transplanted with contaminated bone marrow (BM) generally have a poor outcome. Whether this is also the case when peripheral blood progenitor cell (PBPC) grafts are used is not known. Forty-three patients with chemosensitive DLBCL or follicular lymphoma grade 3 (FLgr3) were treated with high-dose therapy (HDT) and autologous stem cell support. Nine patients received purged grafts. Quantitative real-time polymerase chain reaction (QRT-PCR) for either the BCL2/IgH translocation or allele specific oligonucleotide (ASO) QRT-PCR for the immunoglobulin heavy chain (IgH) complementarity-determining region 3 were used. Nine of 25 (36%) PBPC grafts contained tumour cells as tested by QRT-PCR, including two grafts purged by CD34(+) cell enrichment combined with B-cell depletion. The level of contamination of the PBPC/CD34(+) cells ranged from 0 to 8.28%. No relationship could be shown between the total number of tumour cells infused and relapse. Patients receiving PCR-positive or PCR-negative PBPC grafts had similar progression-free survival (PFS) (P = 0.49). However, a significant difference was seen in PFS and overall survival (OS) for the patients given >/=6.1 x 10(6) CD34(+) cells/kg compared with those given <6.1 x 10(6) CD34(+) cells/kg (P = 0.01 and P < 0.05 respectively).
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PMID:Infused CD34 cell dose, but not tumour cell content of peripheral blood progenitor cell grafts, predicts clinical outcome in patients with diffuse large B-cell lymphoma and follicular lymphoma grade 3 treated with high-dose therapy. 1514 76

Gene expression profiling of diffuse large B-cell lymphoma (DLBCL) has revealed prognostically important subgroups: germinal center B-cell-like (GCB) DLBCL, activated B cell-like (ABC) DLBCL, and primary mediastinal large B-cell lymphoma. The t(14;18)(q32;q21) has been reported previously to define a unique subset within the GCB-DLBCL. We evaluated for the translocation in 141 cases of DLBCL that were successfully gene expression profiled. Using a dual-probe fluorescence in situ hybridization assay, we detected the t(14;18) in 17% of DLBCLs and in 34% of the GCB subgroup which contained the vast majority of positive cases. In addition, 12 t(14;18)-positive cases detected by polymerase chain reaction assays on additional samples were added to the fluorescence in situ hybridization-positive cases for subsequent analysis. Immunohistochemical data indicated that BCL2, BCL6, and CD10 protein were preferentially expressed in the t(14;18)-positive cases as compared to t(14;18)-negative cases. Within the GCB subgroup, the expression of BCL2 and CD10, but not BCL6, differed significantly between cases with or without the t(14;18): 88% versus 24% for BCL2 and 72% versus 32% for CD10, respectively. In the GCB-DLBCL subgroup, a heterogeneous group of genes is overexpressed in the t(14;18)-positive subset, among which BCL2 is a significant discriminator. Interestingly, the t(14;18)-negative subset is dominated by overexpression of cell cycle-associated genes, indicating that these tumors are significantly more proliferative, suggesting distinctive pathogenetic mechanisms. However, despite this higher proliferative activity, there was no significant difference in overall or failure-free survival between the t(14;18)-positive and -negative subsets within the GCB subgroup.
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PMID:BCL2 translocation defines a unique tumor subset within the germinal center B-cell-like diffuse large B-cell lymphoma. 1521 71

Progression of follicular lymphomas (FLs) is often accompanied by a spectrum of histologic changes and an aggressive clinical course. Although molecular alterations have been implicated in this event, the underlying factors are largely unknown. We studied the expression of selected tumor suppressor genes (P53 and retinoblastoma [RB]), oncogenes (MYC and BCL2), and a transferrin-receptor related protein (Trump) in sequential biopsies in 16 patients. Eleven patients progressed from grade I or II FL to aggressive B-cell lymphomas with diffuse morphology, whereas 5 patients presented with diffuse aggressive lymphomas and recurred with indolent lymphomas. Immunoreactivity for P53 correlated with higher histologic grade in lymphomas progressing from indolent to aggressive; however, only 1 patient who presented with aggressive lymphoma demonstrated a P53 gene mutation. Neither P53 immunoreactivity nor genotypic alterations correlated with presentation with an aggressive histology and relapse with FL. Growth fraction, as assessed by Ki-67 staining, and Trump expression correlated with histologic grade. Immunoreactivity for RB, BCL2, and MYC was seldom associated with progression. Eight of 9 cases tested exhibited identical immunoglobulin heavy and light chain rearrangements or identical BCL2 gene rearrangements in the sequential lymphomas. We conclude that P53 and Trump protein expression and proliferation activity correlate with histologic grade, but not with recurrence or progression of FL. Our results further indicate that progression of FL to diffuse aggressive lymphomas and presentation of an aggressive B-cell lymphoma followed by FL are clonally related.
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PMID:Immunophenotypic and genotypic characterization of progression in follicular lymphomas. 1535 33

The present study aimed to characterize the clinical and molecular-cytogenetic features of non-Hodgkin's lymphoma (NHL) with double translocation of the immunoglobulin heavy chain (IGH) gene. G-banding analysis, fluorescence in situ hybridization (FISH) with the IGH (Cgamma and VH) and oncogene (c-MYC, BCL1, BCL2, and BCL6) probes, and long-distance polymerase chain reaction (LD-PCR) were performed on 6 patients with B-cell lymphoma, one with angioimmunoblastic T-cell lymphoma, and one with acute lymphoblastic leukemia (ALL) with B-cell phenotype. G-banding analysis detected two different 14q32 translocations, t(14,18) and add (14)(q32) in a patient with ALL. Two distinct partners of double IGH translocation identified by FISH were as follows: c-MYC + BCL2 in 3 patients, c-MYC + BCL1 in 2, c-MYC + BCL6 in one, BCL2 + 9q22 in one, and 1q21 + 6q27 in one. Colocalization of BCL1 and c-MYC probes was demonstrated in a patient with mantle cell lymphoma. LD-PCR detected c-MYC/Cmu, c-MYC/Calpha and BCL6/Cmu, and c-MYC/Calpha fusion in each one patient. Seven of 8 patients showed high serum LDH. Central nervous system and leukemic involvement was observed in 5 and 6 patients, respectively. Median survival time of patients with c-MYC/IGH translocation was 9 months. The results defined a clinical subset of B-cell lymphoma/leukemia showing extremely poor prognosis. C-MYC/IGH translocation is possibly an evolutionary alteration following the primary IGH translocation with BCL1, BCL2, or BCL6. Furthermore, FISH identified one novel (9q22) and one cryptic chromosomal breakpoints (6q27) involved in IGH translocation.
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PMID:Molecular-cytogenetic characterization of non-Hodgkin's lymphoma with double and cryptic translocations of the immunoglobulin heavy chain gene. 1537 Feb 7

A 72-year-old man was admitted to our hospital to undergo a novel small-intestinal endoscopic procedure. He had had occasional episodes of hematochezia over a 2-year period, during which he had been hospitalized twice previously. However, numerous investigations, including hematological and biochemical studies, gastroscopy, colonoscopy, computed tomography, scintigraphy, and angiography had failed to detect the source of bleeding in the gastrointestinal tract. On this admission, double-balloon enteroscopy was performed and revealed several ulcer scars with localized dilation of the ileum. Histopathological examination of the biopsy specimens revealed no abnormal findings. Partial resection of the ileum was performed to prevent further gastrointestinal bleeding, and histopathological examination of the resected specimen revealed aggregation of atypical lymphocytes, predominantly in the muscularis propria layer. Immunohistochemical examination demonstrated that the tumor cells were positive for CD20 and BCL2, but negative for UCHL1. Based on these findings, the lesion was diagnosed as a marginal-zone B-cell lymphoma of mucosa-associated lymphoid tissue. Eighteen months after surgery, the patient was still in complete remission.
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PMID:Ileal mucosa-associated lymphoid tissue lymphoma showing several ulcer scars detected using double-balloon endoscopy. 1552 Sep 25

The BCL-2 family has been implicated in the pathogenesis of various hematopoietic malignancies, including follicular non-Hodgkin lymphoma and B-cell chronic lymphocytic leukemia. To identify genes that act synergistically in BCL2-enforced leukemogenesis, we developed a murine B-cell lymphoma/leukemia model based on the IL-3-dependent Balb/C pro-B line (FL5.12). FL5.12 cells were stably transfected with antiapoptotic BCL-2 alone or in combination with proapoptotic BAX or nonfunctional mutant BAX, thereby creating various levels of imbalance within the BCL-2 family. Transfectants were intravenously injected into normal Balb/C mice. Whereas FL5.12 cells did not provoke leukemia, mice injected with stable transfectants died of leukemia over time. Disease incidence and latency time depended on the degree of imbalance in the BCL-2 family, supporting a model whereby BCL2 drives tumorigenesis. All mice presented with hepatosplenomegaly and leukemic FL5.12 cells in peripheral blood and bone marrow compartments. Leukemic conversion was accompanied by secondary genetic aberrations leading to clonal IL-3-responsive leukemia. Cellular transformation was independent of alterations in c-Myc or downstream apoptotic pathway. Leukemic clones retained a normal DNA damage response leading to elevated P53 and P21 levels and cell cycle arrest upon irradiation. In conclusion, our mouse model may prove a valuable tool to identify genes that cooperate in BCL2-enforced lymphoma/leukemogenesis.
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PMID:Novel murine B-cell lymphoma/leukemia model to study BCL2-driven oncogenesis. 1564 25

We identified the human germinal center-associated lymphoma (HGAL) in gene-expression profiling studies of diffuse large B-cell lymphoma (DLBCL). The expression of HGAL correlated with survival in patients with DLBCL. The HGAL gene is the human homolog of M17, a mouse gene expressed specifically in normal germinal center (GC) B cells. We generated a monoclonal antibody against the HGAL protein and show that HGAL is expressed in the cytoplasm of GC lymphocytes and in lymphomas of GC derivation. Among 727 lymphomas tested by immunohistochemistry on tissue microarrays, HGAL staining was found in follicular lymphomas (103 of 107), Burkitt lymphomas (40 of 40), mediastinal large B lymphomas (7 of 8), and in DLBCLs (103 of 151). Most marginal zone lymphomas lacked HGAL staining. Lymphocyte-predominant Hodgkin lymphomas (12 of 17) and, surprisingly, classical Hodgkin lymphomas (78 of 107) were found to be positive. Hierarchical clustering of comparative immunohistologic results in DLBCLs demonstrates that the expression of HGAL is similar to 2 other GC-associated proteins, BCL6 and CD10, but different from 2 markers associated with a non-GC phenotype, MUM1/IRF4 and BCL2. The restricted expression and GC specificity of HGAL protein suggest that it may have an important role in the diagnosis of specific lymphomas, and, potentially in the identification of subtypes associated with different prognoses.
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PMID:Expression of the human germinal center-associated lymphoma (HGAL) protein, a new marker of germinal center B-cell derivation. 1567 69

In contrast to nodal large B-cell lymphomas, recurrent chromosomal aberrations have been studied only in a small number of cases of primary cutaneous diffuse large B-cell lymphoma (PCDLBCL). We investigated 25 PCDLBCLs (classified according to the WHO-EORTC classification into PCDLBCL, leg-type, 8; and PCDLBCL, other, 17), using an interphase fluorescence in situ hybridization technique. All cases were analyzed for chromosomal aberrations commonly observed in nodal large B-cell lymphomas, including structural aberrations of the genes BCL2, BCL6, and c-MYC, and numerical aberrations of the chromosomes/genes 3, 7, 8, 11, 12, 13, 17, 18q, RB1, and p53. We observed genetic aberrations in 19 (76%) of 25 patients. The most frequent numerical aberrations were gains of chromosome 12 (7 of 25, 28%), 7 (5 of 25, 20%), 3 (5 of 25, 20%), 18q (3 of 25, 12%), 11 (3 of 25, 12%), X (3 of 25, 12%), and losses of chromosome/gene 17/p53 (3 of 25, 12%). BCL2, c-MYC, and BCL6 were rearranged with the IGH gene in 4 (16%), 1 (4%), and none (0%) of 25 cases, respectively. Most aberrations were homogeneously distributed among cases of PCDLBCL, leg-type and of PCDLBCL, other, cases located on the leg or at other body sites, cases with round and cleaved cell morphology, and Bcl-2+ and Bcl-2- cases. These results suggest that PCDLBCLs show similar chromosomal aberrations irrespective of classification, anatomic site, cell morphology, and Bcl-2 expression, and that many similarities between primary cutaneous and nodal diffuse large B-cell lymphomas can be observed.
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PMID:Genetic aberrations in primary cutaneous large B-cell lymphoma: a fluorescence in situ hybridization study of 25 cases. 1583 92


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