Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present a patient with stage III de novo diffuse large B-cell lymphoma. The lymphoma cells showed mature B-cell immunophenotype but lacked surface immunoglobulin (Ig) expression. Long-distance and long-distance inverse polymerase chain reaction assays to detect the oncogene/Ig gene rearrangement revealed that the cells carried 3 independent fusion genes, namely, c-MYC/Ig heavy chain gene (IgH), BCL2/IgH, and Ig lambda light chain gene/BCL6. Thus, the lymphoma cells concurrently carried t(8;14)(q24;q32), t(14;18)(q32;q21), and t(3;22)(q27;q11), which developed in association with class switching, V/D/J recombination, and somatic hypermutation, respectively. The lymphoma responded to chemoradiotherapy, and the patient has been well for 2 years, suggesting that multiple oncogene rearrangements may not necessarily be associated with poor clinical outcome.
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PMID:Coexistent rearrangements of c-MYC, BCL2, and BCL6 genes in a diffuse large B-cell lymphoma. 1497 79

Hepatitis C virus (HCV) is a nonretroviral oncogenic RNA virus, which is frequently associated with hepatocellular carcinoma (HCC) and B cell lymphoma. We demonstrated here that acute and chronic HCV infection caused a 5- to 10-fold increase in mutation frequency in Ig heavy chain, BCL-6, p53, and beta-catenin genes of in vitro HCV-infected B cell lines and HCV-associated peripheral blood mononuclear cells, lymphomas, and HCCs. The nucleotide-substitution pattern of p53 and beta-catenin was different from that of Ig heavy chain in HCV-infected cells, suggesting two different mechanisms of mutation. In addition, the mutated protooncogenes were amplified in HCV-associated lymphomas and HCCs, but not in lymphomas of nonviral origin or HBV-associated HCC. HCV induced error-prone DNA polymerase zeta, polymerase iota, and activation-induced cytidine deaminase, which together, contributed to the enhancement of mutation frequency, as demonstrated by the RNA interference experiments. These results indicate that HCV induces a mutator phenotype and may transform cells by a hit-and-run mechanism. This finding provides a mechanism of oncogenesis for an RNA virus.
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PMID:Hepatitis C virus induces a mutator phenotype: enhanced mutations of immunoglobulin and protooncogenes. 1499 97

L-PHA reactive oligosaccharides are found on the surface of HBL-2 cells, a lymphoma cell line, established from a human diffuse large B cell lymphoma (DLBCL). Swainsonine (SW) is a potent inhibitor of alpha-mannosidase II which catalyzes the biosynthesis of complex type N-linked oligosaccharides in human cells. CD40L stimulation of HBL-2 cells leads to their prolonged survival. Reduction in the expression of N-linked oligosaccharides, including L-PHA reactive oligosaccharides, on the cell surface by SW treatment resulted in enhancement of HBL-2 cell survival by CD40L stimulation. From an Annexin V assay the enhancement of CD40L-mediated HBL-2 cell survival by SW treatment may have resulted from anti-necrotic effects after 48 h of incubation. Bcl-2 enzyme linked immuno sorbent assay (ELISA) data showed that the expression of bcl-2 protein was enhanced by CD40L stimulation alone and also by CD40L stimulation along with SW treatment. However, there were no significant differences in the amount of bcl-2 protein with these treatments. Therefore, the enhancement of CD40L-mediated cell survival by SW treatment did not depend on the enhancement of bcl-2 protein expression. Furthermore, SW treatment of HBL-2 cells led to degradation of the heavy chain of IgM and rescued HBL-2 cells from anti-IgM-induced growth inhibition. Anti-IgM induced growth inhibition of HBL-2 cells prevented the inhibition of cell death by CD40L. From the present results it is possible that reduction of N-glycosylation of the heavy chain of IgM by SW treatment may reduce anti-IgM-induced growth inhibition, and reduction in anti-IgM-induced growth inhibition due to altered N-glycosylation may enhance CD40-CD40L-mediated cell survival through TRAF2 which interacts with both IgM and CD40 in HBL-2 cells.
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PMID:Regulatory roles of N-glycosylation of immunoglobulin M in CD40-CD40L-mediated cell survival of human diffuse large B cell lymphoma. 1506 43

Follicular mycosis fungoides (MF) is an uncommon histological variant of MF characterized by infiltrates of atypical lymphocytes around and within the epithelium of the hair follicles (folliculotropism). Here we report a patient with rapidly progressive follicular MF on the face, associated with concurrent typical MF lesions elsewhere. The histology was unusual, as apart from dense lymphoid infiltrates showing folliculotropism and epidermotropism, there was a prominent B-cell component with germinal centres, leading to an initial diagnosis of cutaneous B-cell lymphoma. The final diagnosis of follicular MF was established on demonstration of clonal T-cell receptor gene arrangements and lack of clonality for heavy chain gene rearrangements. This case illustrates a variant of MF that has a more rapid progression than the otherwise indolent course of classical MF over many years, and the diagnostic pitfalls, whereby the histology can mimic a B-cell proliferative disorder.
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PMID:Follicular mycosis fungoides mimicking a cutaneous B-cell lymphoproliferative disorder. 1525 Sep 2

ZAP-70 is a tyrosine kinase expressed in normal T cells and NK cells. Expression of ZAP-70 has been associated with poor prognosis in B-cell chronic lymphocytic leukemia and might be a surrogate marker for immunoglobin heavy chain (IGH) mutational status in that disease. Little is known about ZAP-70 expression in other hematologic malignant neoplasms. We examined 446 specimens representing a range of hematopoietic malignant neoplasms for ZAP-70 expression by immunohistochemical analysis. As expected, most T cell-lineage disorders and a subset of small lymphocytic lymphomas were positive. IGH mutational status corresponded to ZAP-70 expression in a small subset of small lymphocytic lymphoma cases subjected to sequence analysis. Of note, however, ZAP-70 was expressed in a minority of other types of B-cell lymphomas, including precursor B-cell acute lymphoblastic leukemia, diffuse large B-cell lymphoma, mantle cell lymphoma, and very rare cases of classic Hodgkin lymphoma. Immunohistochemical analysis represents an alternative method for assessing ZAP-70 expression and reveals that other B-cell malignant neoplasms express ZAP-70.
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PMID:ZAP-70 expression in B-cell hematologic malignancy is not limited to CLL/SLL. 1548 57

Immunoproliferative small intestinal disease (IPSID) was recently added to the growing list of infectious pathogen-associated human lymphomas. Molecular and immunohistochemical studies demonstrated an association with Campylobacter jejuni. IPSID is a variant of the B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), which involves mainly the proximal small intestine resulting in malabsorption, diarrhea, and abdominal pain. Geographically, IPSID is most prevalent in the Middle East and Africa. IPSID lymphomas reveal excessive plasma cell differentiation and produce truncated alpha heavy chain proteins lacking the light chains as well as the first constant domain. The corresponding mRNA lacks the variable heavy chain (V(H)) and the constant heavy chain 1 (C(H)1) sequences and contains deletions as well as insertions of unknown origin. The encoding gene sequence reveals a deletion of V region and parts of C(H)1 domain. Cytogenetic studies demonstrated clonal rearrangements involving predominantly the heavy and light chain genes, including t(9;14) translocation involving the PAX5 gene. Early-stage IPSID responds to antibiotics (30%-70% complete remission). Most untreated IPSID patients progress to lymphoplasmacytic and immunoblastic lymphoma invading the intestinal wall and mesenteric lymph nodes, and may metastasize to a distant organ. IPSID lymphoma shares clinical, morphologic, and molecular features with MALT lymphoma, lymphoplasmacytic lymphoma, and plasma cell neoplasms.
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PMID:Immunoproliferative small intestinal disease (IPSID): a model for mature B-cell neoplasms. 1554 84

The idiotype (Id)-granulocyte-macrophage colony-stimulating factor (GM-CSF) fusion proteins are potential vaccines for immunotherapy of B-cell lymphoma. In this study, four vaccine candidates were constructed by fusing murine GM-CSF to the amino- or carboxy-terminus of the 38C13 murine B-lymphocyte Id scFv with two different arrangements of the variable regions of the heavy chain and light chain (VL-VH and VH-VL). scFv (VH-VL) and GM-CSF/scFv fusion proteins were expressed in an Escherichia coli cell-free protein synthesis system. In order to promote disulfide bond formation during cell-free expression, cell extract was pretreated with iodoacetamide (IAM), and a sulfhydryl redox buffer composed of oxidized and reduced glutathione was added. The E. coli periplasmic disulfide isomerase, DsbC, was also added to rearrange incorrectly formed disulfide linkages. The 38C13 B-lymphocyte Id scFv was expressed with 30% of its soluble yield in active form (43 microg/ml) when tested with an anti-idiotypic mAb, S1C5, as the capture antibody in radioimmunoassay. It was found that the amino-terminal GM-CSF fusion proteins, GM-VL-VH and GM-VH-VL, showed much higher activity than the carboxy-terminal GM-CSF fusion proteins, VL-VH-GM and VH-VL-GM, in stimulating the cell proliferation of a GM-CSF-dependent cell line, NFS-60. Between the two amino-terminal GM-CSF fusion proteins, GM-VL-VH showed a higher total and soluble yield than GM-VH-VL.
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PMID:Rapid expression of vaccine proteins for B-cell lymphoma in a cell-free system. 1566 88

Primary mediastinal B-cell lymphoma (PMBL) is a highly aggressive tumour with a unique pattern of clinical, morphological, immunological and genetic features distinct from other diffuse large B-cell lymphomas. PMBLs are characterized by a mature B-cell phenotype, but they typically lack immunoglobulin (Ig) gene expression. The PMBL cell line MedB-1 shares many characteristic properties of the primary tumour, including low-level Ig production despite a functionally rearranged IgVH gene and absence of 'crippling' mutations. In this study, a search was undertaken for reasons for downregulated Ig expression. Similar levels of the B-cell-specific transcription factors BOB.1/OBF.1 and PU.1 were found in MedB-1 cells to those in the Ig-producing UM-1 lymphoblastoid cell line. However, MedB-1 lacked the Oct2 transcription factor. Reporter assays showed that Ig-type promoters were active in MedB-1 cells. In contrast, activity of the intronic heavy chain enhancer was dramatically reduced. Ectopic expression of Oct2 was able partially to restore enhancer activity but transcription from the endogenous IgVH gene could not be rescued. Therefore, the role of epigenetic factors in the downregulation of Ig was investigated. Methylated histone 3 lysine 9, a reliable marker of chromatin silencing, was not detected in MedB-1 promoter and enhancer regions. Inhibition of DNA methyltransferase and of histone deacetylases also did not reactivate Ig production. These data suggest the existence of alternative mechanisms of Ig inhibition in MedB-1 cells, different from chromatin silencing and the lack of Oct2.
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PMID:Downregulation of internal enhancer activity contributes to abnormally low immunoglobulin expression in the MedB-1 mediastinal B-cell lymphoma cell line. 1568 41

We report the case of a 79-year-old woman with a longstanding lymphedema of the right arm who developed a skin lymphoma involving the right wrist area. Microscopically, the lesion was composed of numerous centroblasts infiltrating both the dermis and the subcutaneous tissue. Phenotypic investigations showed expression of CD20, CD79a, and bcl-2 protein by neoplastic cells. In addition, these cells were CD5 positive. No expression of anaplastic large cell lymphoma kinase (ALK), CD10, CD23, CD30, CD43, bcl-6, cyclin D1, p53 or p16INK4a could be seen. Polymerase chain reaction (PCR) analysis demonstrated a clonal rearrangement of the genes coding for the kappa light chain of the immunoglobulin (Ig). No rearrangement of the genes coding for the Ig heavy chain, t(14;18) or t(11;14) chromosome translocations, or Epstein-Barr virus (EBV) genomic sequences could be found. The tumor was classified as stage IE and was first cured by complete surgical excision. Nineteen months later, a recurrence was noted in the right elbow area. This study further illustrates that lymphoma of the skin may complicate chronic limb lymphedema. Like most of the previously reported cases, this neoplasm belonged to the category of diffuse large B-cell lymphoma. However, it showed CD5 expression as a singular feature.
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PMID:De novo CD5-positive diffuse large B-cell lymphoma of the skin arising in chronic limb lymphedema. 1601 18

Pyothorax-associated lymphoma (PAL) is a B-cell lymphoma which develops in the pleural cavity of patients with an over-20-year history of pyothorax. Aberrant expression of surface antigens is occasional in PAL, although genotype is not fully investigated. We report here a PAL with dual genotype, i.e., simultaneous immunoglobin (Ig) and T-cell receptor (TcR) gene rearrangement. An 82-year-old woman with pain on the left side of the chest was admitted. She had been suffering from pyothorax after artificial pneumothorax for treatment of tuberculosis of the pulmonary when she was 18 years old. The mass that was confined to the left pleural cavity affected by pyothorax was biopsied and histologically diagnosed as diffuse large cell lymphoma. The tumor cells were positive for CD20, CD16, and TIA-1 but negative for CD79a, CD45RO, CD43, CD3, and CD56. Surface antigen expression was further investigated in cultured cells, showing that the cultured cells did not express representative B-cell markers, except for CD20, as well as T-cell markers, but were positive for CD16, CD30, and CD103. Southern blotting revealed the monoclonally rearranged bands of both Ig heavy chain and TcR gene. The patients died of tumors 14 months after admission. Aberrant genotype and immunophenotype of PAL cells is discussed in reviewing the pertinent literature.
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PMID:Pyothorax-associated lymphoma: an unusual case with both T- and B-cell genotypes. 1602 7


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