14 results on '"Mason, David Y."'
Search Results
2. The expression of Bcl-2 by proliferating cells varies in different categories of B-cell lymphoma.
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Masir, Noraidah, Jones, Margaret, Lee, Abigail M., Goff, Lindsey K., Clear, Andrew J., Lister, Andrew, Marafioti, Teresa, and Mason, David Y.
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HISTOPATHOLOGY , *CELL proliferation , *LYMPHOMAS , *LYMPHOPROLIFERATIVE disorders , *CELL growth - Abstract
Masir N, Jones M, Lee A M, Goff L K, Clear A J, Lister A, Marafioti T & Mason D Y (2010) Histopathology 56, 617–626 The expression of Bcl-2 by proliferating cells varies in different categories of B-cell lymphoma Aims: To investigate the relationship between Bcl-2 protein expression and cell proliferation at single-cell level in B-cell lymphomas using double-labelling techniques. Methods and results: The relationship between Bcl-2 protein expression and cell proliferation was explored in 124 cases of B-cell lymphoma using double immunofluorescence labelling for Bcl-2 and Ki67. In follicular lymphoma, marginal zone lymphoma and a subset of chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL), neoplastic cells tended to lose Bcl-2 when they are in cell cycle. This pattern is usually maintained in both follicular lymphoma and CLL/SLL when they undergo high-grade transformation. In mantle cell lymphoma, diffuse large B-cell lymphoma and a subset of CLL/SLL, the inverse relationship (between Bcl-2 and Ki67) was not observed, i.e. the proliferating cells tended to show co-expression of Bcl-2. Conclusions: In low-grade lymphomas, including those that are transformed, Bcl-2 expression is lost when cell proliferate. However, in more aggressive tumours (i.e. mantle cell and de novo diffuse large B-cell lymphomas) the inverse Bcl-2/Ki67 relationship was not observed. It would be of interest to explore the clinical implications in lymphoma of the presence and absence of the inverse Bcl-2/Ki67 pattern. [ABSTRACT FROM AUTHOR]
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- 2010
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3. Ribosome-associated nucleophosmin 1: increased expression and shuttling activity distinguishes prognostic subtypes in chronic lymphocytic leukaemia.
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Rees-Unwin, Karen S., Faragher, Robin, Unwin, Richard D., Adams, Julie, Brown, Philip J., Buckle, Ann-Marie, Pettitt, Andrew, Hutchinson, Claire V., Johnson, Suzanne M., Pulford, Karen, Banham, Alison H., Whetton, Anthony D., Lucas, Guy, Mason, David Y., and Burthem, John
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CHRONIC lymphocytic leukemia , *ANTIBODY diversity , *IMMUNOGLOBULIN genes , *APOPTOSIS , *GENETIC mutation , *PROTEIN synthesis - Abstract
Two distinct groups of chronic lymphocytic leukaemia (CLL) are distinguished by the presence or absence of somatic hypermutation of the immunoglobulin heavy-chain gene. CLL without somatic hypermuataion has an adverse outcome, but the precise biological differences that underlie this more aggressive clinical-course are unclear. Using a proteomic approach, we found that the two prognostic forms of CLL were consistently distinguished according to their protein expression pattern. The most important difference observed related to the different expression of nucleophosmin 1 between the two forms of CLL. This different expression was not related to apoptosis, proliferation or gene mutation. However, co-immunoprecipitation experiments identified an association between nucleophosmin 1 and ribosomal proteins. Using immunocytofluorescence, nucleophosmin 1 expression was identified in the nucleoli and nucleoplasm of all cells, but in a proportion of cells, nucleophosmin had been transferred from the nucleoplasm to the cytoplasm. Both the fluorescent intensity, and the frequency of cytoplasmic nucleophosmin 1 expression, was higher in CLL without somatic hypermutation. We propose therefore, that nucleophosmin 1, in association with ribosomal proteins, undergoes nucleo-cytoplasmic shuttling in CLL. This process is most prominent in un-mutated CLL and may signify altered protein biosynthesis. [ABSTRACT FROM AUTHOR]
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- 2010
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4. BCL2 protein expression in follicular lymphomas with t(14;18) chromosomal translocations.
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Masir, Noraidah, Campbell, Lisa J., Goff, Lindsey K., Jones, Margaret, Marafioti, Teresa, Cordell, Jacqueline, Clear, Andrew J., Lister, T. Andrew, Mason, David Y., and Lee, Abigail M.
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DENDRITIC cells , *EPITOPES , *IMMUNOFLUORESCENCE , *CELL proliferation , *NUCLEOTIDE sequence , *LYMPHOMAS , *GENETICS - Abstract
The t(14;18)(q32;q21) chromosomal translocation induces BCL2 protein overexpression in most follicular lymphomas. However the expression of BCL2 is not always homogeneous and may demonstrate a variable degree of heterogeneity. This study analysed BCL2 protein expression pattern in 33 cases of t(14;18)-positive follicular lymphomas using antibodies against two different epitopes (i.e. the widely used antibody BCL2/124 and an alternative antibody E17). 16/33 (49%) cases demonstrated strong BCL2 expression. In 10/33 (30%) cases, BCL2 expression was heterogeneous and in some of these, its loss appeared to be correlated with cell proliferation, as indicated by Ki67 expression. Double immunofluorescence labelling confirmed an inverse BCL2/Ki67 relationship, where in 24/28 (86%) cases cellular expression of BCL2 and Ki67 was mutually exclusive. In addition, seven BCL2 ‘pseudo-negative’ cases were identified in which immunostaining was negative with antibody BCL2/124, but positive with antibody E17. Genomic DNA sequencing of these ‘pseudo-negative’ cases demonstrated eleven mutations in four cases and nine of these were missense mutations. It can be concluded that in follicular lymphomas, despite carrying the t(14;18) translocations, BCL2 protein expression may be heterogeneous and loss of BCL2 could be related to cell proliferation. Secondly, mutations in translocated BCL2 genes appear to be common and may cause BCL2 pseudo-negative immunostaining. [ABSTRACT FROM AUTHOR]
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- 2009
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5. Frequent epigenetic silencing of protocadherin 10 by methylation in multiple haematologic malignancies.
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Jianming Ying, Zifen Gao, Hongyu Li, Srivastava, Gopesh, Murray, Paul G., Hwee Koon Goh, Chai Yen Lim, Yajun Wang, Marafioti, Teresa, Mason, David Y., Ambinder, Richard F., Chan, Anthony T. C., and Qian Tao
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TUMORS , *TUMOR suppressor genes , *CANCER , *LYMPHOMAS , *BLOOD plasma - Abstract
Epigenetic silencing of tumour suppressor genes (TSG) inactivates TSG functions. Previously, we identified PCDH10 as a methylated TSG in carcinomas. Here, we detected its frequent silencing and methylation in lymphoma cell lines including 100% Burkitt, 100% diffuse large B cell, 86% Hodgkin, 100% nasal natural killer/T-cell lymphoma and 1/3 of leukaemia cell lines, and in primary tumours but not in normal peripheral blood mononuclear cells or lymph nodes. PCDH10 silencing could be reversed by demethylation with 5-aza-2′-deoxycytidine. Methylation was further detected in 14% of Hodgkin lymphoma sera. Thus, PCDH10 methylation is frequently involved in lymphomagenesis and could serve as a tumour-specific biomarker. [ABSTRACT FROM AUTHOR]
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- 2007
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6. The NFATc1 transcription factor is widely expressed in white cells and translocates from the cytoplasm to the nucleus in a subset of human lymphomas.
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Marafiot, Teresa, Pozzobon, Michela, Hansmann, Martin-Leo, Ventura, Roland, Pileri, Stefano A., Roberton, Helen, Gesk, Stefan, Gaulard, Philippe, Barth, Thomas F. E., Du, Ming Q., Leoncini, Lorenzo, Möller, Peter, Natkunam, Yasodha, Siebert, Reiner, and Mason, David Y.
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LEUCOCYTES , *LYMPHOID tissue , *TRANSCRIPTION factors , *LYMPHOMAS , *GENETIC transformation , *HODGKIN'S disease , *PLASMA cell diseases , *T cells , *CELL proliferation - Abstract
Stimulation of lymphoid cells via their surface receptors triggers signalling pathways that terminate in the nucleus, where they induce alterations in gene transcription. Nuclear factor of activated T cells (NFAT) transcription factors, involved in a major Ca2+-dependent signalling pathway, normally reside in the cytoplasm but re-locate to the nucleus when activation of the pathway (e.g. following ligation of antigen receptors) leads to their dephosphorylation. This study found that one member of the NFAT family (NFATc1/NFAT2) can be detected in routine biopsy samples, where it is seen in essentially all lymphoid cells, but is absent from the great majority of non-haematopoietic cells. An immunohistological evaluation of NFATc1 in almost 300 lymphomas showed that most neoplastic lymphoid cells also express NFATc1 as a cytoplasmic constituent, although it is absent in classical Hodgkin's disease and plasma cell proliferations. Of particular interest was the finding that NFATc1 was relocated to the nucleus in a minority of lymphoid neoplasms (usually diffuse large B-cell lymphomas or Burkitt lymphoma), presumably reflecting activation of the NFAT pathway. It would be of interest to correlate this feature with patterns of gene expression and also with prognosis, since it may identify a subset of human lymphoma that is distinct in its molecular and clinical features. [ABSTRACT FROM AUTHOR]
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- 2005
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7. Expression pattern of FCRL (FREB, FcRX) in normal and neoplastic human B cells.
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Masir, Noraidah, Jones, Margaret, Pozzobon, Michela, Marafioti, Teresa, Volkova, Olga Y., Mechetina, Ludmila V., Hansmann, Martin-Leo, Natkunam, Yasodha, Taranin, Alexander V., and Mason, David Y.
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LYMPHOCYTES , *IMMUNOGLOBULIN G , *LYMPHOID tissue , *IMMUNOGLOBULINS , *IMMUNE system , *LYMPH nodes - Abstract
FCRL (also known as FREB and FcRX) is a recently described member of the family of Fc receptors for immunoglobulin G (IgG). In the present study we analysed its expression in normal and neoplastic lymphoid tissue using immunohistochemical techniques. FCRL was preferentially expressed in a proportion of germinal centre cells and, more weakly, in mantle zone B cells. In addition, strong labelling was observed in marginal zone B cells in the spleen, representing one of the few markers for this cell type. The majority of cases of small B-cell lymphoma, diffuse large B-cell lymphoma and lymphocyte predominance Hodgkin's disease were positive for FCRL. However, the number of positive cells varied widely, and in consequence we could not define a cut-off that distinguished subsets of diffuse large B-cell lymphoma. Our results also showed that FCRL tended to be negative in T-cell-rich B-cell lymphoma and in classical Hodgkin's disease. FCRL may therefore represent a novel marker for normal B cells (e.g. splenic marginal zone cells) and may also be useful as a potential marker of B-cell neoplasms. [ABSTRACT FROM AUTHOR]
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- 2004
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8. research paper Intracellular signalling molecules as immunohistochemical markers of normal and neoplastic human leucocytes in routine biopsy samples.
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Pozzobon, Michela, Marafioti, Teresa, Hansmann, Martin-Leo, Natkunam, Yasodha, and Mason, David Y.
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LEUCOCYTES , *IMMUNOHISTOCHEMISTRY , *BIOPSY , *PHOSPHOLIPASES , *MOLECULES , *IMMUNOGLOBULINS , *LYMPHOCYTES - Abstract
We have investigated whether intracellular signal transduction molecules can be used as immunohistological markers of normal and neoplastic human leucocytes in routine tissue sections. We obtained selective labelling of white cells for eight such molecules (the ‘linker’ molecules SLP-76 and BLNK, the Src family kinases Lyn, Fyn, Syk and Hck, and the phospholipases PLC- γ1 and PLC- γ2). Antibodies to SLP-76 and PLC- γ1 selectively labelled T cells, and antibodies to BLNK, Lyn, Fyn, Syk and PLC- γ2 labelled B cells (although Fyn immunostaining was restricted to mantle zone B cells). Antibodies to the Syk and Hck kinases labelled probable thymocyte precursors at the periphery of the thymic cortex. In addition to lymphoid cells, several other leucocyte types were immunostained (e.g. SLP-76, Lyn, Syk and Hck were found in megakaryocytes, myeloid cells and/or macrophages, and PLC- γ2 was detected in arterial endothelium). SLP-76 and PLC- γ1 were found in most T-cell lymphomas studied, and some B-cell lymphomas were also positive for PLC- γ1 (e.g. diffuse large cell and Burkitt's lymphoma). The five B cell-associated markers were found in most B-cell non-Hodgkin's lymphomas, although some diffuse large B-cell lymphomas were negative (e.g. for Lyn) and anti-Fyn tended not to stain small B-cell neoplasms. The observation that a range of leucocyte signalling molecules can be detected in routine biopsies offers new possibilities for studying normal and neoplastic human white cells in diagnostic tissue samples. [ABSTRACT FROM AUTHOR]
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- 2004
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9. Detection by the fluorescence in situ hybridization technique ofMYC translocations in paraffin-embedded lymphoma biopsy samples.
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Haralambieva, Eugenia, Banham, Alison H., Bastard, Christian, Delsol, Georges, Gaulard, Philippe, Ott, German, Pileri, Stefano, Fletcher, Jonathan A., and Mason, David Y.
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FLUORESCENCE in situ hybridization , *LYMPHOMAS , *BIOPSY - Abstract
The detection of chromosomal translocations by fluorescence in situ hybridization (FISH) is widely performed, but very few studies have attempted to apply this technique to paraffin-embedded routine biopsy samples. We report the analysis of paraffin sections from 36 B-cell lymphoma biopsies for MYC translocation breakpoints by FISH. The probes consisted of multi-YAC constructs that flanked the breakpoint region and that, therefore, separate upon a chromosomal translocation and generate split (or 'segregated') signals (rather than a more ambiguous 'co-localization' pattern, obtained when the two partners in a hybrid gene are detected). The results were assessed by a simple approach that avoids the counting of signal numbers per nucleus and so is appropriate for use in routine practice. A total of 19 of the 36 lymphomas were scored as positive for MYC translocation and this included 16 of the 20 patients in whom classic cytogenetics had shown the presence of the (8;14) translocation (or one of its two variants). We conclude that this two-colour 'split-signal' technique based on breakpoint flanking probes can readily detect chromosomal translocations in paraffin sections. Furthermore, our results suggest that cases categorized as 'atypical Burkitt's/Burkitt-like' lymphoma (at least for adult patients) are heterogeneous with respect to translocations involving the MYC oncogene, as well as immunophenotype and clinical features. [ABSTRACT FROM AUTHOR]
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- 2003
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10. Leucocyte-specific protein (LSP1) in malignant lymphoma and Hodgkin's disease.
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Marafioti, Teresa, Jabri, Lamia, Pulford, Karen, Brousset, Pierre, Mason, David Y., and Delsol, Georges
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BLOOD proteins , *LEUCOCYTES , *LYMPHOMAS , *HODGKIN'S disease - Abstract
Summary. Biopsies from 319 haematopoietic neoplasms were immunostained for intracellular leucocyte-specific protein 1 (LSP1) to assess its distribution and to compare its diagnostic value with that of CD45 (leucocyte common antigen: LCA). Most small B-cell neoplasms expressed LSP1, but one third of diffuse large B-cell lymphomas (DLBCL) were LSP1 negative. Among the cases with DLBCL (76 samples) tested for both LSP1 and CD45, one fifth expressed only CD45, but five samples were LSP1-positive and negative for CD45. The latter pattern was also seen in four of nine myelomas. Five out of 14 T-lymphoblastic lymphomas co-expressed LSP1 and CD45, and three cases were LSP1 negative and CD45-positive. Most peripheral T-cell lymphomas co-expressed LSP1 and CD45. All anaplastic lymphoma kinase (ALK)-negative lymphomas of anaplastic large cell morphology (T and null phenotype) expressed LSP1 although the percentage of LSP1-positive tumour cells was variable, however, only seven out of 30 cases with ALK-positive lymphoma were LSP1 positive. LSP1 was expressed on Reed–Sternberg cells in 60 out of 66 cases with classic Hodgkin's disease but neoplastic cells were usually negative in lymphocyte predominant Hodgkin's. This study confirms the wide expression of LSP1 within haematopoietic neoplasms and its diagnostic value for a minority of lymphoid tumours that have lost CD45 expression. Furthermore, the strong expression of LSP1 in classic Hodgkin's disease, contrasting with its heterogeneous expression in ALK-negative anaplastic lymphomas, may help to distinguish the latter lymphomas from patients with tumour cell-rich Hodgkin's disease. [ABSTRACT FROM AUTHOR]
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- 2003
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11. Immunochemical studies of antigenic lymphoma-associated proteins.
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Pulford, Karen, Roberton, Helen, Banham, Alison H, Hatton, Christian S. R, and Mason, David Y
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LYMPHOMAS , *PROTEIN kinases , *ONCOGENES , *IMMUNOCHEMISTRY - Abstract
Summary. We have previously reported that plasma from patients with anaplastic lymphoma kinase (ALK)-positive lymphoma contains antibodies against the oncogenic kinase NPM-ALK protein characteristic of this disease. We investigated whether this reactivity represents a phenomenon unique to ALK-positive lymphoma by screening plasma from patients with follicular lymphoma for antibodies to BCL-2 protein. Eight out of 10 samples showed such reactivity (and in six cases gave specific staining of BCL-2-transfected cells). As these findings suggest a new biochemical approach to the identification of oncogenic proteins in lymphoma, we investigated whether antibodies present in patients with ALK-positive lymphoma can precipitate NPM-ALK in quantities which should be sufficient for further analysis. We found that plasma samples from all10 patients studied immunoprecipitated NPM-ALK asaprotein visible in silver-stained sodium dodecyl sulphatepolyacrylamide gels. Finally we demonstrated that NPM-ALK could be visualized more clearly if it were immunoprecipitated from extracts of cells in which newly synthesized proteins had been labelled with 35 S and then identified by autoradiography. These results suggest a strategy for using patients' autoantibodies to screen for antibodies to other tumour-associated proteins. [ABSTRACT FROM AUTHOR]
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- 2002
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12. Anaplastic large-cell lymphomas of B-cell phenotype are anaplastic lymphoma kinase (ALK) negative and belong to the spectrum of diffuse large B-cell lymphomas.
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Haralambieva, Eugenia, Pulford, Karen A. F., Lamant, Laurence, Pileri, Stefano, Roncador, Giovanna, Gatter, Kevin C., Delsol, Georges, and Mason, David Y.
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LYMPHOMAS , *PHENOTYPES - Abstract
There is controversy in the literature as to whether anaplastic large-cell lymphoma of B-cell phenotype is related to the t(2;5)-positive T- or ‘null’ cell lymphoma of the same morphology. We report a study of 24 lymphomas with morphological features of anaplastic large-cell lymphoma which expressed one or more B-cell markers and lacked T-lineage markers. Clinical features were more in keeping with large B-cell lymphoma than with classical t(2;5)-positive anaplastic large-cell lymphoma, and immunostaining for anaplastic lymphoma kinase (ALK) protein provided no evidence for the (2;5) translocation (or one of its variants). The staining patterns for CD20 and CD79 were typical of diffuse large B-cell lymphoma, CD30 expression was variable, and most cases (15/22) lacked epithelial membrane antigen (EMA). These findings support the view that ‘B-cell anaplastic large-cell lymphoma’ is unrelated to t(2;5)-positive (ALK‐positive) lymphoma, and that it represents a morphological pattern occasionally encountered among diffuse large B-cell lymphomas. By the same reasoning, most tumours diagnosed as ‘ALK‐negative anaplastic large‐cell lymphoma of T‐cell or null phenotype’ probably belong to the spectrum of peripheral T‐cell lymphomas. [ABSTRACT FROM AUTHOR]
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- 2000
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13. Kupffer cell staining by an HFE-specific monoclonal antibody: implications for hereditary haemochromatosis.
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Bastin, Judy M, Jones, Margaret, O'callaghan, Christopher A., Schimanski, Lisa, Mason, David Y., Townsend, Alain R. M., and Bastin, Judy
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MONOCLONAL antibodies , *PROTEINS , *HEMOCHROMATOSIS - Abstract
Hereditary haemochromatosis is an inherited disorder of iron absorption that leads to excessive iron storage in the liver and other organs. A candidate disease gene HFE has been identified that encodes a novel MHC class I like protein. We report the development of a monoclonal antibody (HFE-JB1) specific for recombinant refolded HFE protein. The antibody immunoprecipitates a 49 kD protein from the cell line U937, a histiocytic lymphoma. It binds HFE but does not recognize other recombinant non-classic MHC class I proteins (HLA-E, F and G), nor does it react with a variety of recombinant classic class I MHC molecules. COS cells transfected with HFE in culture are stained specifically. The immunohistochemical staining pattern in human tissues is unique and can be defined as a subset of the transferrin receptor positive cells. In the liver HFE protein was shown to be present on Kupffer cells and endothelium (sinusoidal lining cells), but absent from the parenchyma. Kupffer cells from an untreated C282Y HH patient failed to stain with the antibody. In the normal gut scattered cells in the crypts are stained. HFE was also present on capillary endothelium in the brain (a site of high levels of transferrin receptor) and on scattered cells in the cerebellum and cortex. These results raise interesting questions concerning the function of HFE in the control of body iron content and distribution. [ABSTRACT FROM AUTHOR]
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- 1998
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14. The t(2;5)-associated p80 NPM/ALK fusion protein in nodal and cutaneous CD30+ lymphoproliferative disorders.
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Su, Lyndon D., Schnitzer, Bertram, Ross, Charles W., Vasef, Mohammad, Mori, Shigeo, Shiota, Mami, Mason, David Y., Pulford, Karen, Headington, John T., and Singleton, Timothy P.
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SKIN diseases , *CELLS , *REPRODUCTION , *LYMPHOMAS , *RETICULOENDOTHELIAL granulomas , *CHROMOSOMAL translocation - Abstract
A high percentage of extra cutaneous CD3O+ anaplastic large cell lymphomas (nodal ALCL) carry a specific chromosomal translocation, t(2;5) (p23;q35), that results in abnormal expression of p80 NPM/ALK chimeric protein (p80). The protein p80 may be detected by immunohistochemistry using polyclonal (anti-p80) or monoclonal (ALK1) antibody directed against the ALK epitope. Although nodal ALCL, primary cutaneous ALCL, and lyrnphomatoid papulosis type A (lyp A) have similar histologic and immunohistochemical features, the expression of p80 in these cutaneous lesions has not been extensively studied. We immunostained tissues from 10 nodal ALCL, 8 primary cutaneous ALCL, 24 lyp A, and positive and negative controls using polyclonal rabbit anti-p80 and the avidin-biotin-peroxidase labeling method. Reactivity was determined by comparing staining intensity to positive controls [4 nodal ALCL with t(2;5)] and negative controls (21 non-ALCL lymphomas). Only cutaneous lesions staining positively with anti-p80 were further studied with the monoclonal antibody ALK1 and reverse transcription polymerase chain reaction (RT-PCR) for p80 messenger RNA. All positive controls (4/4), but none of the negative controls (0/21) nor lyp A (0/24), were immunoreactive for anti-p80. Sixty percent (6/ 10) of nodal ALCL and a single case (12%) of primary cutaneous ALCL were immunoreactive for anti-p80. In this exceptional cutaneous lesion, although we did not find NPM/ALK by RT-PCR, we detected strong expression of ALK using ALK1. We conclude that t(2;5) is rarely involved in the pathogenesis of cutaneous CD3O+ lymphoproliferative disorders. [ABSTRACT FROM AUTHOR]
- Published
- 1997
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