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Biomedical subjects

M F Greaves

Publications and source records attributed to M F Greaves.

At least 163 records · Page 9Linked to original sources
PubMed1982

5'nucleotidase, adenosine deaminase and purine nucleoside phosphorylase activities in acute leukaemia.

Three enzymes concerned in purine degradation, 5'nucleotidase (5'NT), adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) have been measured biochemically in the bone marrow or peripheral blood blasts from 75 patients with acute leukaemia, from 18 patients with blast crisis of chronic granulocytic leukaemia and in the bone marrow and peripheral blood lymphocytes from 14 normal donors. Characteristic patterns among the different sub-types of acute leukaemia have been detected, with high ADA, low 5'NT and PNP in Thy-ALL, high 5'NT and ADA in c-ALL, high PNP and low ADA in AML. The cells in CGL blast transformation resembled the enzymatic pattern of either AML or c-ALL respectively. However, no significant correlation was found between any pair of enzymes in any group of leukaemia, normal bone marrow or peripheral blood lymphocytes studied here.

Acute Disease↗
PubMed1982

Monoclonal antibodies defining markers with apparent selectivity for particular haemopoietic cell types may also detect antigens on cells of neural crest origin.

Monoclonal antibodies described as reacting with particular subsets of haemopoietic cells were screened against a variety of neuronal cell lines to further investigate their true specificity. While some reagents, e.g., monoclonal anti-cALL (J5), were found only reactive with haemopoietic cells, other monoclonals, e.g., BA1, BA2, NA134, OKT6, and OKT9, also bound to neuronal cells. Further investigation into the cross-reactivity of these antibodies to a variety of neural crest derived cell lines indicated that, with the exception of OKT9, differential binding patterns to different lines were obtained. This suggests that haemopoietic cell subsets and neural crest derived tissues can share similar differentiation antigens. For monoclonals OKT9 and BA2 this observation was confirmed biochemically, showing that it is not just antigenic determinants but similar molecular weight cell surface antigens that are shared between subsets of the two major cell types. A similar analysis using monoclonal antibodies raised against human neuronal cells or cell lines again indicates that some antigens appear unique to neural tissue while others are shared by haemopoietic cell subsets.

Antibodies, Monoclonal↗
PubMed1982

The membrane phenotype of T-prolymphocytic leukaemia.

Cells from 13 cases of T-prolymphocytic leukaemia (T-PLL) were studied with a battery of immunological techniques in order to define their membrane phenotype. All cases were E-rosette positive and were negative with OKT6, anti-HLA-DR, anti-Ig and M-rosettes; in 3, 20-30% of the cells had receptors for C3b. 7 cases had predominantly a 'helper/inducer' T-subset phenotype, (OKT4+, OKT8-) and 4 had a 'suppressor/cytotoxic' phenotype (OKT8+, OKT4-). Cells in 2 cases coexpressed OKT4 and OKT8 in 48% and 95% of prolymphocytes and in another, both OKT4 and OKT8 were negative. Terminal transferase (TdT) was negative by IF in all the cases, but a low positive level was detected biochemically in one. Although T-PLL appears to be heterogenous in respect of membrane phenotype, the observation of unexpected features in 8 of the cases raises the possibility that it may originate in a cell of intermediate maturation between late thymocytes and mature T-lymphocytes. These features plus the clinical manifestation of the disease - typical morphology, splenomegaly, lymphadenopathy, skin lesions, high WBC and aggressive clinical course - help define T-PLL as a distinct clinicopathological entity.

Aged↗
PubMed1982

Changes in cell surface antigen expression during hemopoietic differentiation.

Human bone marrow cells were separated on a fluorescence activated cell sorter (FACS) according to their binding of a series of monoclonal antibodies; the positive and negative fractions were cloned for erythroid burst and colony-forming units (BFU-E and CFU-E) and myeloid colony-forming units (CFU-GM), and cytocentrifuge slides were prepared for microscopy of maturing precursors. The pattern of antigen expression on hemopoietic progenitor and precursor populations has been established using antibodies defining blood group (A, I/i), HLA-associated (*A, B, C, DR, DC1), lineage specific, and transferrin receptor antigens. Like monomorphic HLA-DR, the antigen defined by monoclonal antibody OKT10 is expressed on the earliest progenitors and lost during differentiation, suggesting a role in interactions regulating the differentiation of these cells. The HLA-linked DC1 determinant, in contrast to HLA-DR, is not expressed at a detectable level on progenitor cells. Although a lineage-specific early antigen has not been identified, the transferrin receptor is expressed on the majority of erythroid progenitors, but only weakly on myeloid progenitors, and may provide an approach to isolating erythroid progenitors. These and earlier studies with monoclonal antibodies against HLA-DR and glycophorin now provide a detailed "map" of antigen expression during hemopoietic differentiation.

ABO Blood-Group System↗
PubMed1982

Characterization of HLA-DR antigens on leukaemic cells.

A large series of leukaemias (1,512 cases) and leukaemic cell lines (40) have been tested for selective expression of a monomorphic HLR-DR determinant using a monoclonal antibody (DA2). Relatively mature myeloid leukaemias (APML, CGL) and erythroid leukemias are DR-, in contrast to most (72% leukaemias of myeloid precursors (e.g. AML) which are DR+. Non-T ALL are DR+ but T (thymic) ALL are invariably DR-. In contrast to the latter, some leukaemias with mature T cell phenotypes are DR+. Leukaemias or lymphomas of B cells and B cell precursors (e.g. pre-BALL) are invariably DR+, whereas myeloma or plasma cell leukaemias are DR-. This pattern of selective expression appears to closely parallel that seen in normal haemopoietic differentiation. Biochemical features of HLA-DR structures on leukaemic cells have been compared with the known features of B cell derived DR molecules and in one case ALL compared with an autologous (EBV transformed) B cell line. Most leukemic cells showed the same general alpha and beta two chain structure. However, B cell line and most chronic leukaemias showed the presence of an extra band of molecular weight 30,000 daltons (p30) with an intermediate electrophoretic mobility on SDS-PAGE between that of the alpha and beta DR chains. In acute leukaemias and leukaemic cell lines (i.e. immature cells) p30 was not seen unless short labelling times were used. Two dimensional NEPHGE/SDS-PAGE under appropriate labelling conditions showed that the pattern of spots obtained from an ALL line (Nalm-6) and its autologous EBV transformed partner (B85) were similar though not identical. Pulse chase labelling of Nalm-6 and B85 showed that the turnover rate of p30 relative to DR alpha and beta chains, differed in the two lines.

Antigens, Neoplasm↗
PubMed1982

Phenotypic diversity of T cell leukemias.

A series of monoclonal antibodies and additional selective markers (e.g. TdT) have been used to describe the detailed composite phenotypes expressed by cells in 172 cases of T cell leukemia. The results provide further evidence for a striking correlation between phenotype, maturation arrest, and clinical subgroup, and have important implications for our understanding of the origins of T cell malignancy.

Adult↗
PubMed1981

Partial maturation and light chain restriction of Abelson virus-transformed B cell precursors.

The induction of partial maturation in an in vitro derived Abelson virus-transformed murine lymphoid cell subline (ABC-1/AT1) is described. Pre-B (cytoplasmic, mu chain-positive) lymphocytes were induced from presumptive B cell precursors by prostaglandin E1, butyric acid, lipopolysaccharide and interferon. Maturation was independent of alterations in cellular growth rate and could be achieved in the absence of cell division. The AT1 subline was found to be restricted to the expression of a single light chain type (lambda) indicating a possible B cell lineage-committed precursor as the target for viral transformation.

Abelson murine leukemia virus↗
PubMed1981

The aplastic presentation of childhood leukaemia: a feature of common-ALL.

Transient pancytopenia preceded the onset of acute leukaemia in eight of 360 (2%) of children with acute lymphoblastic leukaemia (ALL) but did not occur in 70 cases of acute non-lymphoblastic leukaemia. The patients developed overt leukaemia within 5-38 weeks of first presentation with features of marrow failure. Immunological classification of blast cells was performed in six of the eight patients and all had phenotype of common-ALL (c-ALL). We conclude that the sydnrome of pre-leukaemia aplasia in childhood is a feature of c-ALL.

Blood Cell Count↗
PubMed1981

A monoclonal antibody detecting an antigen shared by neural and granulocytic cells.

A monoclonal antibody, MI/N1, is described that reacts predominantly with fresh neuroblastoma tissue, human neuroblastoma cell lines, and cells of the myeloid lineage. Investigation of the binding of this antibody to four different neuroblastoma cell lines showed CHP 100 bound approximately 4 times more antibody than CHP 126. Only 30% of the cells in the line CHP 100 bound MI/N1 as determined by indirect immunofluorescence. Thus, both quantitative and qualitative differences in the expression of antigen recognised by MI/N1 are detected on human neuroblastoma cell lines. Inasmuch as only five of eight marrow aspirates heavily infiltrated with neuroblasts bound the monoclonal, this also suggests a heterogeneity in antigenic expression on fresh tumour cells. Absorption studies indicate that the antigen recognised by MI/N1 is present on human foetal brain and adult human cerebellum. At a dilution of 1/750, equal volumes of foetal brain and adult cerebellum absorbed out 30 and 60% of the reactivity to the human neuroblastoma cell line CHP 100. No reactivity was found towards murine neuroblastoma cells or rat brain. Expression of antigen on cells in the myeloid lineage appears dependent upon their stage of maturation, increasing as cells mature to neutrophils and eosinophils. It is suggested that the quantitative and qualitative differences seen in the expression of antigen on neuroblastoma cells may relate to their being blocked at different stages of differentiation.

Adult↗
PubMed1981

The biochemical characterization of a cell surface antigen associated with acute lymphoblastic leukemia and lymphocyte precursors.

The acute lymphoblastic leukemia- (ALL) associated membrane antigen is a single glycosylated polypeptide of approximate m.w. of 100,000 (gp100), containing no intrachain disulfide linkages. Approximately 50% of gp100 will bind to lentil lectin, whereas 100% will bind to the lectin from Ricinus communis. Both lentil-binding and lentil nonbinding forms of the antigen appear to be identical by 2-dimensional isoelectric focusing/SDS polyacrylamide gel electrophoresis and peptide mapping. Carbohydrate, although contributing approximately 20 to 25% of the m.w., appears not to be involved in the antigenic site of the ALL antigen as judged by precipitation of a molecule after tunicamycin treatment of cells or glycosidase digestion. Charge shift electrophoresis and labeling with the lipophilic nitrene reagent hexanoyl diiodo-N-(4-azido-2-nitrophenyl)-tyramine suggests that the cALL antigen is probably not an integral membrane protein; however, it remains tightly bound to the plasma membrane after subcellular fractionation. A glycoprotein of the same m.w. has been detected by immunoprecipitation on bone marrow cells of nonleukemic patients. serologic studies indicate that the cALL-associated antigen is found on the terminal transferase-positive lymphoid cells, and it therefore seems likely that the gp100 molecule is a normal gene products of lymphocyte precursors.

Animals↗
PubMed1981

Immunologically defined subclasses of acute lymphoblastic leukaemia in children: their relationship to presentation features and prognosis.

Leukaemic cells from 542 patients under 21 years of age with a diagnosis of acute lymphoblastic leukaemia (ALL) were typed with immunological cell surface markers between June 1975 and December 1979; 379 of these patients entered into the trials up until December 1978 have been followed for more than 1 year. They were divided into four subgroups: common (c) ALL, T (thymic) ALL, 'null' (or 'unclassified') ALL and a rare lymphoma/leukaemia type B-ALL. A T-cell phenotype was found more frequently in boys and was usually but not invariably associated with a high white cell count at presentation. A mediastinal thymic mass was present in 53% of T-ALL patients but was not observed in any unequivocal not-T ALL. Clinical prognosis differed substantially between the three major phenotypic classes, remission induction rate and remission duration being lowest in T-ALL, better in 'null' ALL, and highest in cALL (P trend less than 0 . 0001; P = 0 . 0002 for comparison of cALL versus T-ALL). There was a much higher incidence of CNS involvement in the T-ALL group than in the cALL group or 'null' All group and although this was strongly correlated with WBC count it was also significantly associated with T-ALL independent of WBC count. Overall in this series and also within the major cALL subclass there is a strong correlation between high WBC count and poor clinical response (remission induction and duration). When the three major immunological subclasses are adjusted for WBC count the prognostic correlation of antigenic phenotype is reduced and statistically insignificant. It is suggested that immunological (and enzymatic) phenotype of ALL subclasses may not be an independent correlate of prognosis but nevertheless is linked to other cell differentiation features, especially growth rate and sites of clonal expansion (e.g. marrow versus thymus), which critically influence the size of the clonogenic leukaemic population and its associated evolutionary status with the respect to drug resistant mutants at the time of diagnosis and introduction of therapy.

Adolescent↗
PubMed1981

Exploitation of monoclonal antibodies: a "who's who" of haemopoietic malignancy.

A library of monoclonal antibodies plus "conventional' markers (e.g. anti-TdT) have been used to explore the detailed phenotypes of leukaemic cells in relation to normal haemopoietic differentiation. This analysis reveals that consistent, composite phenotypes of different subclasses of lymphoid malignancies closely mimic those of corresponding normal cells at equivalent levels of maturation. It is suggested that three major target cell populations are available for lymphoid malignancy: the pluripotential stem cell (e.g. "lymphoid' blast crisis of CGL), lymphoid progenitors or stem cells in the bone marrow (non-T ALL) or thymus (T-ALL, T-NHL) and long lived, mature and immunocompetent T and B cells (T-CLL, PLL, Sézary and B-CLL, lymphoma respectively). The major phenotypes documented in different leukaemias represent the level of "maturation arrest' imposed on the dominant subclone; this is determined by, but not necessarily synonymous with, the "target cell' and associated clonogenic cell population in the leukaemia. No consistent major abnormalities of gene expression are revealed by this investigation and although they may exist (e.g. loss or acquisition of antigens with malignant progression) we suggest that they are irrelevant to the central issue of what alterations are essential and sufficient for the evolution of clonogenic leukaemic cells. We propose instead that subtle changes, which uncouple proliferation and differentiation, are all that is required.

Antibodies, Monoclonal↗