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

Discordant bone marrow (BM) involvement in patients with a diagnosis of large-cell non-Hodgkin's lymphoma (NHL) is characterized by marrow infiltrates predominantly composed of small lymphoid cell, cytologically compatible with low-grade NHL. Although this phenomenon is well described morphologically, molecular data concerning the relationship of the two lesions are lacking. The aim of the study was to investigate the clonal relationship of discordant lymphoma manifestations by using immunoglobulin heavy chain gene (IgH), as well as bcl-2 rearrangements, as molecular markers. IgH rearrangements were amplified by PCR with consensus primers directed against framework regions 3 or 2 (FR3 and FR2), followed by automated fragment length analysis and sequencing in selected cases. Rearrangements of the bcl-2 gene were identified with primers against the major breakpoint region. Small BM infiltrates were isolated by laser capture microdissection. In addition, immunohistochemistry was performed on paraffin sections using antibodies against CD3, CD10, CD20, bcl-2, bcl-6, p53, and the Ki67 antigen. Paraffin-embedded tissues of 21 cases diagnosed as diffuse large B-cell lymphoma (DLBCL) with discordant BM involvement and no previous history of low-grade B-cell NHL were analyzed. After review of immunohistochemical stains, 5 cases were excluded either as concordant BM infiltrates by large-cell lymphoma with abundant reactive T-cells (2 cases) or as benign, reactive lymphoid infiltrates (3 cases), as confirmed by a polyclonal pattern in the IgH analysis. Of the remaining 16 cases, a common clonal origin was confirmed in 8 cases by the presence of an identical clonal IgH rearrangement or bcl-2 rearrangement. In 4 cases, identification of distinct IgH or bcl-2 rearrangements gave evidence for the presence of two clonally unrelated neoplasms. The remaining 4 cases were not evaluable for technical reasons. Morphological, phenotypical, and molecular findings were compatible with a lymphoma of germinal center origin in the majority of cases. However, in 4 cases, flow cytometric analysis of the BM infiltrates revealed a B-cell chronic lymphocytic leukemia phenotype. Two of these cases were clonally related to the DLBCL and thus represented Richter's transformation. In summary, discordant BM infiltrates in DLBCL represent a heterogeneous group of disorders, encompassing cases with a clonally related, clinically occult small-cell component, as well as cases with two clonally distinct, unrelated B-cell neoplasms presenting synchronously at different locations.
 ...
PMID:Discordant bone marrow involvement in diffuse large B-cell lymphoma: comparative molecular analysis reveals a heterogeneous group of disorders. 1253 91

In the World Health Organization classification system, splenic marginal-zone lymphoma (splenic MZL) is described as an indolent B-cell lymphoma, which generally presents as splenomegaly with involvement of the bone marrow and peripheral blood. Presence of disease in peripheral lymph nodes and extranodal locations is uncommon. Splenic MZL is characterised by micronodular infiltration of the spleen with marginal-zone differentiation; the immunophenotype is usually IgM+ IgD+/- cytoplasmic-Ig-/+ pan B antigens+ CD5- CD10- CD23- CD43-/+ cyclin D1-; and the most common genetic abnormalities are deletions at 7q22-7q32. Most patients with splenic MZL live for a long time but classic prognostic factors cannot distinguish between patients who are likely to have good and poor outcomes. However, immunological events, such as haemolytic anaemia and immune thrombocytopenia, or the presence of a monoclonal component, are significantly associated with shorter survival. Splenectomy is considered the first-line treatment of choice for splenic MZL; it results in only partial remission, but responses are generally sufficient for correcting cytopenia, improving quality of life, and increasing survival.
 ...
PMID:Splenic marginal-zone lymphoma: a distinct clinical and pathological entity. 1257 51

Coexpression of CD5 and CD10 is highly unusual in B-cell lymphomas and may pose a diagnostic challenge. We report 42 cases of B-cell lymphoma with simultaneous expression of CD5 and CD10. They made up approximately 0.4% of all B-cell lymphomas seen during the study period and included the following cases: large B-cell lymphoma (LBCL), 14 (33%); follicular lymphoma (FL), 10 (24%); mantle cell lymphoma (MCL), 9 (21%); chronic lymphocytic leukemia, 4 (10%); acute precursor B-cell lymphoblastic leukemia/lymphoma, 2 (5%); and other low-grade B-cell lymphomas, 3 (7%). All MCLs had overexpression of bcl-1 or the t(11;14) and were CD43+. All FLs had typical histomorphologic features and were bcl-2+ and bcl-6+ but CD43-. Of 14 LBCLs, 5 were histologically high-grade. Six (43%) of 14 patients with LBCL died within 10 months of diagnosis of CD5+CD10+ lymphoma (median survival, 4 months), including all 3 patients with stage IV disease and 2 of 5 with histologically high-grade lymphoma. Our findings indicate that coexpression of CD5 and CD10 is rare but occurs in diverse subtypes of B-cell lymphoma. Investigation of bcl-1, bcl-6, and CD43 and morphologic evaluation may resolve the potential confusion in diagnosis and lead to the recognition of the correct lymphoma subtype.
 ...
PMID:B-cell lymphomas with coexpression of CD5 and CD10. 1257 92

Crystal-storing histiocytosis (CSH) is a rare disorder occurring in patients with lymphoproliferative diseases, predominantly in cases of multiple myeloma and low-grade B-cell lymphoma. To the best of our knowledge, only three cases of pulmonary CSH have been reported in the English literature and one of them was associated with a low-grade B-cell lymphoma (immunocytoma). We document a case of a 59-year-old man with bilateral lung masses in which a right middle lobe pulmonary lobectomy specimen showed CSH associated with an extranodal marginal-zone B-cell lymphoma. A single nodule showing features of fibroleiomyomatous hamartoma was present in a wedge biopsy specimen from the left lung. Two nodules within the right middle lobe were composed of sheets of histiocytic cells with abundant eosinophilic cytoplasm resembling striated muscle cells. In addition, there were nodular aggregates and a more diffuse infiltrate of small slightly atypical centrocyte-like lymphocytes, as well as bronchial lymphoepithelial lesions. Immunohistochemistry performed on paraffin-embedded sections demonstrated that the histiocytic cells were immunoreactive with the KP-1 (CD68) antibody while the lymphocytic infiltrate was CD20 positive, co-expressed for CD43, and was negative for CD3, CD5, and CD10. Genotypic analysis demonstrated the presence of an immunoglobulin heavy-chain gene rearrangement, indicating the presence of a monoclonal B-cell population. These features were consistent with pulmonary CSH associated with extranodal marginal-zone lymphoma of baltoma type.
 ...
PMID:Pulmonary crystal-storing histiocytosis and extranodal marginal zone B-cell lymphoma associated with a fibroleiomyomatous hamartoma. 1261 74

Patients with diffuse large B-cell lymphoma (DLBCL) rarely show relapse after 4 years of complete remission (CR). In this study, we addressed the following questions: (1) Does late-relapsing DLBCL represent clonally related disease or a second malignancy; and (2) is there a characteristic biologic background? In 10 of 13 DLBCL patients with relapse after 4 to 17 years, a clonal relationship was established based on identical IgH-sequences and/or identical bcl2-IgH translocation. Most (77%) showed features of germinal center (GC) cells, as defined by expression of CD10, bcl-2, and bcl-6 protein and ongoing immunoglobulin heavy chain variable region (VH) hypermutation. A GC phenotype was seen in 8 (20%) of 38 control patients matched for age, stage, and (extra)nodal localization with relapse within 2.5 years (P =.005). In conclusion, we have found evidence that late-relapsing DLBCL represents truly clonally related disease episodes in most cases and that this clinical behavior may be related to the biologic features of GC cells.
 ...
PMID:Very late relapse in diffuse large B-cell lymphoma represents clonally related disease and is marked by germinal center cell features. 1264 52

A 36-year-old man presented with a red nodule on his left shoulder. Histologically, there were variously sized, irregularly shaped nests throughout the dermis partly extending into the subcutaneous tissue. Masses of centrocyte-like cells were situated in the center of the tumor nests and accompanied by adjacent secondary follicle structures. Partial follicular colonization was seen. Massive plasmacytoid cells were located in the papillary dermis and the periphery of the tumor nests. Immunohistochemically, these centrocyte-like cells were positive for CD19 and alkaline phosphatase, and negative for CD5 and CD10. Cytoplasm of the plasmacytoid cells was positive for IgG and lambda-light chain, and negative for IgM, IgA, and kappa-light chain. Monotypic immunoglobulin staining including light chain restriction was shown. Clonal immunoglobulin heavy chain gene rearrangement by Southern blot analysis was shown in the tumor tissue. Morphologic, immunohistochemical, and molecular studies revealed that this patient had a cutaneous marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type. Electron beam (total 40 Gy) irradiation was applied. The tumor disappeared completely. Neither local recurrence or metastasis have appeared during 3 years of follow-up.
 ...
PMID:Cutaneous marginal zone B-cell lymphoma: a case accompanied by massive plasmacytoid cells. 1273 86

The great majority of primary central nervous system lymphoma (PCNSL) is known to be of B-lineage, with T-cell PCNSL (T-PCNSL) accounting for <5%. We report an unusually high incidence of T-cell lymphoma among the PCNSLs originated in a large general-care hospital in the metropolitan Seoul area. PCNSLs (n = 42) accrued from April 1995 through June 2001 were reviewed for histologic and clinical features, and immunohistochemical staining was done for CD3, CD20, CD4, CD8, Bcl-6, and CD10. Clonal rearrangements of the TCR-gamma and IgH genes were studied with semi-nested PCR in all seven cases of T-PCNSL and seven of 35 B-cell PCNSL (B-PCNSL). Formalin-fixed, paraffin-embedded specimens were used in all these studies. By immunohistochemical staining and molecular studies, seven cases (16.7%) were diagnosed as T-PCNSL, each displaying clonal rearrangement of the TCR-gamma gene, and 35 (83.3%) as B-PCNSL. Radiologically, T-PCNSL was significantly correlated with the superficial and subcortical lobar location (p <0.001), solitary mass formation (p = 0.001), presence of rim enhancement (p <0.001), and peritumoral edema (p = 0.029). Involvement of cerebrospinal fluid was observed only in B-PCNSL (n = 17) but not in T-PCNSL (p = 0.010). Histologically, T-PCNSL was characterized by a population of mixed predominantly small- and occasionally medium-sized cells (p <0.001), which were loosely scattered without forming a solid mass (p = 0.024), and perivascular infiltration was frequent (p = 0.007), in contrast to predominantly large cells of B-PCNSL, i.e., diffuse large B-cell lymphoma (DLBCL), in which the cells tended to aggregate to form monomorphous sheets (p = 0.024). In T-PCNSL, staining for CD8 was positive in five, including one with coexpression of CD4, and two were negative for CD4 and CD8. Of 24 DLBCLs tested, the pattern of Bcl-6+ tumor cells was diffusely dense, similar to that of the germinal center in nine cases (37.5%), with coexpression of CD10 in three of the nine cases. T-PCNSL accounted for 16.7% of the PCNSLs; thus, in Korea it may not be as rare as previously known. The T-PCNSL presented with certain clinical and pathologic features that were distinct from B-PCNSL and displayed preponderance of CD8 expression. DLBCL of the germinal center B-cell derivation defined by bcl-6 expression comprised 37.5% of DLBCL of the brain.
 ...
PMID:Primary central nervous system lymphoma in Korea: comparison of B- and T-cell lymphomas. 1282 84

Expression of Bcl-6 and CD10, markers for the tumor of the germinal center (GC) B-cell derivation, has been studied in primary diffuse large B-cell lymphomas (DLBCLs) of the lymph node, gastrointestinal tract, and mediastinum. In these studies, the coexpression rate of CD10 and Bcl-6 was relatively constant at 30% approximately 40%, but the frequency of Bcl-6+ tumors varied from 55% to 100%, raising doubts about the usefulness of Bcl-6 expression in identifying the tumor of GC B-cell derivation. Because the expression of Bcl-6 in tumors of non-GC B-cell origin has recently been reported, we critically evaluated the expression of Bcl-6 and CD10 in primary DLBCLs of the tonsil, a relatively common tumor in Japan and Korea. The cases (n = 51) represented a consecutive series for any recent 2-year period at several teaching hospitals in Korea and Japan. Formalin-fixed, paraffin-embedded specimens were used for immunostaining. Staining for Bcl-6 and CD10 was positive in 44 (86%) and 22 cases (45%), respectively. However, among those positive for Bcl-6 (>10% Bcl-6+ tumor cells), 2 basic patterns were recognized: uniform and nonuniform. The uniform pattern was characterized by a dense population (>75%) and a consistent density in any given area, resembling the staining pattern observed in GC or follicular lymphoma (FL) (the "GC/FL" pattern). In contrast, the nonuniform pattern exhibited a varying density from area to area, as well as a less-dense population (<75%). The uniform pattern was observed in 26 cases (51%). All but 1 (95%) of the CD10+ tumors coexpressed Bcl-6, with most (82%) displaying the uniform pattern. We conclude that tumors showing a uniform pattern of Bcl-6 expression should be distinguished from those showing a nonuniform pattern, because the former most likely represent tumors of GC B-cell derivation and the latter most likely represent tumors of non-GC derivation. GC B-cell lymphoma thus defined accounted for 51% of tonsillar DLBCL, a proportion comparable to that of the nodal DLBCL. CD10 expression correlated with the "GC/FL" pattern, but appeared to be not essential for the identification of GC B-cell lymphoma. This study suggests that a significant proportion of tonsillar DLBCLs in Asia is of GC B-cell origin rather than of mucosa-associated lymphoid tissue origin. This finding may have significance for clinical management of these lymphomas.
 ...
PMID:Detection of germinal center B-cell lymphoma in archival specimens: critical evaluation of Bcl-6 protein expression in diffuse large B-cell lymphoma of the tonsil. 1282 16

In the new World Health Organization (WHO) classification of malignant lymphoma, anaplastic large cell lymphoma of B-cell phenotype is classified either as the anaplastic large cell variant of diffuse large B-cell lymphoma or as Hodgkin's lymphoma. A 71-year-old Japanese man developed fever and generalized lymphadenopathy. Biopsy of the right axillary node revealed morphology of malignant lymphoma in which large cells with abundant cytoplasm and pleomorphic nuclei were scattered among small lymphocytes. Immunostaining with various monoclonal antibodies revealed the large cells to be CD79+, CD20/L26+, CD45RO/UCHL-(1-), CD3-, CD10-, CD30+, NPM/ALK-, EMA-, CD15-, and bcl-(2-). Amplification of the J region of the immunoglobulin heavy chain by polymerase chain reaction revealed a single rearranged band. Therefore the diagnosis of anaplastic large cell variant of diffuse large B-cell lymphoma, stage IIIB, was made from the standpoint of the new WHO classification of malignant lymphoma. Biopsy led to findings of Epstein-Barr virus (EBV)-associated lymphoma with positive in situ hybridization results for EBV small RNAs, positive results of immunostaining with EBV latent membrane 1 antibody, and negative results of immunostaining with Epstein-Barr nuclear antigen 2. Results of immunostaining of the mass with p53 antibody also were positive for lymphoma cells. The findings in this case may suggest a close relationship between p53 expression and latent EBV infection.
 ...
PMID:Epstein-Barr virus-associated anaplastic large cell variant of diffuse large B-cell-type non-Hodgkin's lymphoma with concurrent p53 protein expression. 1284 89

Traditional chemotherapeutic drugs are often restricted by severe side effects and lack of tumor specificity. Peptide prodrugs cleavable by peptidases present in the tumor environment have been explored to improve the therapeutic index of cytotoxic drugs. One such prodrug of doxorubicin (Dox), CPI-0004Na [N-succinyl-beta-alanyl-L-leucyl-L-alanyl-L-leucyl-Dox (sALAL-Dox)] has been shown to have an improved antitumor efficacy profile with reduced toxicity compared with Dox in tumor xenograft models (V. Dubois et al., Cancer Res., 62: 2327-2331, 2002). In this study, we demonstrate that CD10, a cell surface metalloprotease expressed on a variety of tumor cell types, is capable of cleaving CPI-0004Na and related peptide prodrugs such as N-succinyl-beta-alanyl-L-isoleucyl-L-alanyl-L-leucyl-Dox (sAIAL-Dox). This proteolytic cleavage generates leucyl-Dox, which is capable of entering cells and generating intracellular Dox. In a [(3)H]thymidine proliferation assay, analogues of CPI-0004Na showed a 100-300-fold increase in potency on CD10(+) cells compared with CD10(-) cells. Cytotoxicity of CPI-0004Na was inhibited by phosphoramidon, a known inhibitor of CD10 enzymatic activity. Furthermore, Chinese hamster ovary CHO-S cells, which are resistant to CPI-0004Na, could be sensitized to the cytotoxic effect of the prodrug by transfection of a CD10 cDNA. Tumor xenograft studies using LNCaP prostate tumor cells support the important role of CD10 in the antitumor efficacy of these prodrugs against tumors expressing CD10. CPI-0004Na and sAIAL-Dox achieved statistically significant 70% tumor growth inhibition at day 22. CD10 is expressed on many types of human tumors including B-cell lymphoma, leukemia, and prostate, breast, colorectal, and lung carcinomas; therefore, CD10-cleavable prodrugs may be effective in a range of different tumor types.
 ...
PMID:CD10 is a key enzyme involved in the activation of tumor-activated peptide prodrug CPI-0004Na and novel analogues: implications for the design of novel peptide prodrugs for the therapy of CD10+ tumors. 1450 Mar 90


<< Previous 1 2 3 4 5 6 7 8 9 10