Membrane phenotypic studies in B cell lymphoproliferative disorders.

Scott, Colin; Limbert, Howard J.; MacKarill, I D; Roberts, B. E.

doi:10.1136/jcp.38.9.995

Cited by 22 publications

(3 citation statements)

References 26 publications

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“…[7][8][9][10] LPDs with low or absent CD20, such as B-cell chronic lymphocytic leukemia, are FMC7 negative, while those in which CD20 has high expression, such as hairy-cell leukemia, are FMC7 positive. 2,3,[11][12][13][14][15][16] Binding of FMC7 to patient samples and to B-cell lines is blocked by prior incubation with anti-CD20 antibody, 5,17 indicating apposition of FMC7 and CD20 epitopes. The detection of FMC7 after transfection of CD20 cDNA into a myeloid cell line provided the first direct evidence that FMC7 recognizes CD20.…”

Section: Introductionmentioning

confidence: 99%

A cholesterol-dependent CD20 epitope detected by the FMC7 antibody

et al. 2003

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Accurate diagnosis of lymphoid malignancies is essential for appropriate therapeutic intervention. In conjunction with other diagnostic determinants, immunophenotypic analysis of differentially expressed cell surface markers, such as CD5, CD20, CD23 and FMC7, is useful in the subclassification of lymphomas and leukemias arising from the B-cell lineage. Recent evidence suggesting that CD20 predicts FMC7 expression has prompted reappraisal of the utility of monitoring both markers. Here, we report that the FMC7 monoclonal antibody (mAb) specifically and strongly recognized CD20 ectopically expressed in hematopoietic and nonhematopoietic cell lines. The reactivity of FMC7 was abolished by mutations in the extracellular domain of CD20. These data confirm the CD20 specificity of FMC7. Like other CD20 mAbs, FMC7 binding was temperature dependent and induced detergent insolubility of CD20. Of significant interest, the CD20 epitope recognized by FMC7 was unusual in that it was exceptionally sensitive to membrane cholesterol. Cholesterol depletion profoundly reduced expression of the FMC7 epitope, whereas cholesterol enrichment enhanced its expression. FMC7 mAb binding thus appears to be a sensitive indicator of the level of plasma membrane cholesterol and reveals a conformational state of CD20 that is regulated by cholesterol.

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Section: Introductionmentioning

confidence: 99%

A cholesterol-dependent CD20 epitope detected by the FMC7 antibody

et al. 2003

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“…Immunological studies of CLL and CLL-Pro cases included the demonstration of surface immunoglobulin (SIg) kappa or lambda light chain restriction, together with an assessment of the fluorescent SIg staining intensity, and membrane CDlO (CALLA, Becton-Dickinson: J5, Coulter Electronics), FMC7 (Sera-Lab) and CD23: TUl : Biotest) determinants by indirect immunofluorescence. On the basis of these studies, the immunophenotypic characteristics considered to support a diagnosis of CLL were weak monoclonal surface immunoglobulin (SIg) density (observed in 96 per cent of cases), significant (> 10 per cent) MRBC receptor and CD23 expression, an absence ( < l o per cent positive cells) of detectable membrane CDlO and, in most (76 per cent) cases insignificant FMC7 staining (Scott et al, 1985(Scott et al, , 1987a. For comparison, phenotypic features of CLL-Pro cases differed in that these patients often showed increased SIg densities and/or increased FMC7-positive components (Scott etal., 1987a,b).…”

Section: Patients Studied and Case Classificationmentioning

confidence: 99%

Diagnostic features and survival in typical and prolymphocytoid variants of chronic lymphocytic leukemia

Scott¹,

Stark²,

Head

et al. 1989

Hematological Oncology

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Diagnostic features were evaluated with regards to survival in 203 cases of typical and prolymphocytoid chronic lymphocytic leukemia. Excluding 27 (13 per cent) patients with second malignancies, survival analyses indicated that the prognostic factors with greatest significance were age at presentation (less than 65 years and 65 years or more: p = 0.0004), proportions of prolymphocytoid cells (less than 10 per cent and 10 per cent or more: p less than 0.0001 age corrected) and surface immunoglobulin (SIg) density (weak and more than weak: p = 0.001 age corrected). In contrast, sex, absolute numbers of prolymphocytoid cells, SIg light chain type and FMC7 expression were not prognostically significant. These observations suggest that the recognition and delineation of prolymphocytoid CLL variants by morphological and immunophenotypic criteria, although important in diagnostic terms, may have less relevance with respect to prognosis and patient management.

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“…Based on a hypothetical model ofB-cell ontogeny, non-Hodgkin's lymphomas (NHL) of B-cell lineage are considered as a malignant proliferation of particular differentiation stages in lymphopoiesis. According to this theory, specific antigen expression patterns for defined B-cell lymphoma subtypes were proposed by several authors (Bennett et a[, 1989;Baldini et al, 1990;Nash, 1986: Harris et al 1984Scott et al, 1985;Stein et al, 1984).…”

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confidence: 99%

Immunophenotyping of low‐grade B‐cell lymphoma in blood and bone marrow: poor correlation between immunophenotype and cytological/histological classification

Schwonzen¹,

Pohl²,

Steinmetz³

et al. 1993

Br J Haematol

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Results of immunophenotypic examinations of peripheral blood and/or bone marrow (BM), involved in low-grade B-cell non-Hodgkin's lymphomas, were compared with the results of cytomorphological and histopathological examinations in 133 adult patients. 69 cases of chronic B-lymphocytic leukaemia (B-CLL), 16 centrocytic (CC) lymphomas, 14 centroblastic-centrocytic (CB/CC) lymphomas, 15 immunocytomas (IC), 10 cases of hairy cell leukaemia (HCL), four prolymphocytic leukaemias (PLL), two B-CLL in transformation, one splenic lymphoma with villous lymphocytes (SLVL), one hairy cell leukaemia variant (HCL-V), and one lymphocytic lymphoma (LC) were classified according to the Kiel and/or FAB classification. Leukaemic disease was found in 105 cases. The following markers were used for immunocytology (APAAP technique) of blood and/or BM smears: CD19, CD5, CD10, CD11c, CD14, CD21, CD22, CD23, CD25, CD38 and TdT. All cases tested showed CD19, but no TdT expression. Every case of HCL had a distinct phenotype with expression of CD11c, CD22 and CD25 and the lack of CD5 and CD23 antigens. In all other NHL cases a very heterogenous expression of CD-antigens with no significant correlations to the cytomorphological subtypes was found. The expression of CD5 is a frequent but inconstant finding in lymphoproliferative diseases other than B-CLL, so 50% of CB/CC, 75% of CC and 80% of IC were CD5 positive. Our results indicate that, with the exception of HCL, the diagnostic relevance of immunophenotyping for the classification of cytomorphologically and histopathologically defined subtypes in blood and/or BM is of very limited value.

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Membrane phenotypic studies in B cell lymphoproliferative disorders.

Cited by 22 publications

References 26 publications

A cholesterol-dependent CD20 epitope detected by the FMC7 antibody

A cholesterol-dependent CD20 epitope detected by the FMC7 antibody

Diagnostic features and survival in typical and prolymphocytoid variants of chronic lymphocytic leukemia

Immunophenotyping of low‐grade B‐cell lymphoma in blood and bone marrow: poor correlation between immunophenotype and cytological/histological classification

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