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Biomedical subjects

M F Greaves

Publications and source records attributed to M F Greaves.

At least 217 records · Page 12Linked to original sources

Membrane marker analysis of 'lymphoid' and myeloid blast crisis in PH1 positive (chronic myeloid) leukemia.

The membrane phenotype of leukaemic cells was analysed during different stages of chronic myeloid leukaemia by a panel of markers. These included antisera against ALL antigen, p23,30 (Ia-like structure) and other T cell, B cell and myeloid markers 'Lymphoid' blast crisis shares the phenotype of common ALL (of non-T, non-B variety). Both leukemias react with anti-ALL serum and have pre-myeloid, pre-B lymphoid and pre-thymocyte characteristics. Their phenotype may reflect the characteristics of the pluripotential stem cell from which they derive. Nevertheless both leukaemias retain their undifferentiated characteristics and lack overt myeloid, B cell and thymocyte differentiation markers. Myeloid blast crisis and AML are negative with anti-ALL serum but some of the poorly differentiated myeloblasts react with anti-p23,30 serum (and negative for SmIg). The anti-p23,30 serum (used in a double marker assay combined with anti-immunoglobulin) detects some (4-11%) intermediate sized agranular p23,30+/SmIg-cells in peripheral blood during the chronic phase of CML as well as in normal foetal bone marrow. These could be myeloid stem cells (from which in CML the myeloid blast crisis arises). The results demonstrate that surface membrane analysis can aid exact diagnosis in different stages of CML.

Antigens, Neoplasm↗

A non-T, non-B human leukemia cell line (NALM-1): establishment of the cell line and presence of leukemia-associated antigens.

A permanent hematopoietic cell line, designated NALM-1, was established from the peripheral blood of a patient who was in blastic crisis of Ph1-positive chronic myleocytic leukemia. By means of a panel of specific xenoantisera, the NALM-1 cells were found to express a specific antigen of acute lymphoblastic leukemia and blast leukemia-associated antigen. The cells exhibited no cell-surface receptors for sheep erythrocytes, IgG, or complement; neither cell-surface immunoglobulins nor cytoplasmic immunoglobulin were observed. Furthermore, normal T-cell or B-cell antigens, detectable by the antisera used in this study, were not found in the NALM-1 line.

Antigens, Neoplasm↗

Acid esterase in human lymphoid cells and leukaemic blasts: a marker for T lymphocytes.

A non-specific acid alpha-naphthyl-acetate esterase activity was investigated in human lymphoid cell populations from tonsils, blood, thymus and in different leukaemias. Four patterns have emerged. (i) The vast majority of T lymphocytes (peripheral blood, tonsils) showed a localized, intense reaction product ("T-like"). (ii) A thymocyte subpopulation expressed faint, localized enzyme activity ("Thy-like) but the majority of thymocytes showed no esterase activity. Some cells from acute lymphoblastic leukaemias with thymocyte surface characteristics had a "Thy-like" appearance. (iii) Most B lymphocytes and cells from chronic lymphocytic leukaemias were esterase negative. No activity was seen in mitogen activated peripheral blood T and B lymphoblasts from peripheral blood and in leukaemic blasts from the common form of childhood acute "lymphoblastic" leukaemia. (iv) Myeloid cells, including peripheral blood monocytes, and blast cells from acute myeloblastic and chronic granulocytic leukaemias showed an intense, diffuse reaction product (M-like). It is concluded that the modified esterase technique is a convenient marker for small mature human T lymphocytes in tissue sections and smears. It may also be helpful in the differential diagnosis of acute lymphoblastic leukaemia with T characteristics, the common form of acute "lymphoblastic" leukaemia and acute myeloblastic leukaemia.

Diagnosis, Differential↗

Target cell in chronic myeloid leukaemia and its relationship to acute lymphoid leukaemia.

On the basis of membrane marker analysis with an antiserum made against acute lymphoblastic leukaemia and other immunological markers it is suggested that some chronic myeloid leukaemias (C.M.L.) and some acute lymphoblastic leukaemias (A.L.L.) originate in a common target cell or precursor. This is possibly a pluripotential stem cell or a closely related derivative. These leukaemic cells retain their undifferentiated membrane characteristics C.M.L. patients in blast crisis who are A.L.L.-antigen-positive and have terminal transferase enzyme activity might benefit from therapy usually given in typical Philadelphia-chromosome-negative A.L.L.

Antigens, Neoplasm↗

Studies on the glycolipids of sheep thymus and of normal and concanavalin A-stimulated sheep peripheral lymphocytes.

The neutral glycolipids and gangliosides of sheep thymus and of sheep peripheral lymphocytes were compared. The patterns of both of these major classes of glycolipids were more complex in thymus than in the lymphocytes. The incorporation of radioactivity from D-[1-14C]galactose into the individual glycolipids of control and concanavalin A-stimulated sheep peripheral lymphocytes was also studied. A marked enhancement of incorporation into trihexosylceramide and an alteration of the pattern of incorporation into gangliosides were noted in the mitogen-treated cells. The results suggest that significant alterations of glycolipid composition and metabolism may occur during at least certain stages of lymphocyte differentiation.

Animals↗

Blast crisis of chronic myeloid leukaemia (CML). I. Presentation simulating acute lymphoid leukaemia (ALL).

Seven patients presenting as an acute leukaemia caused difficulty in diagnosis. The lymphoid appearance of the balst cells either initially or during treatment suggested acute lymphoid leukaemia (ALL). In each case the Philadelphia chromosome was shown to be present thus suggesting that these cases were examples of chronic myeloid leukaemia (CML) presenting in blast crisis without a detectable chronic phase. The implications of these findings are discussed and the difficulty in achieving a precise diagnosis in the acute leukaemias is emphasised. Cytogenetic analysis should be carried out whenever the type of acute leukaemia present is of critical importance.

Adolescent↗

Blast crisis of chronic myeloid leukaemia (CML). II. Cell surface marker analysis of "lymphoid" and myeloid cases.

Fourteen cases of philadelphia chromosome (Ph1) positive chronic myeloid leukaemia in blast transformation have been investigated using cell surface markers. Morphologically eight cases were lymphoid and the remainder myeloid in appearance. All cases were negative with surface markers for thymocytes and T and B lymphocytes. Five of the lymphoid cases reacted with an antiserum specific for acute lymphoid leukaemia )ALL) of non-T non-B type and were also weakly reactive with a lymphocyte reactive antiserum. A sixth patient, whose blast cells were anti-ALL negative (ALL-) at presentation, subsequently developed central nervous system leukaemia with anti-ALL positive (ALL+) blast cells in the CSF. In all cases the leukaemic blast cells showed greatly diminished expression of cholera toxin receptors when compared to granulocytic cells from the chronic phase of CML. This parallels weak or negligible expression of the cholera toxin receptor in ALL and AML. These results suggest that the blastic phase of CML may involve different cellular derivatives of a pluripotential stem cell in which the primary malignant/genetic changes reside. The blast crisis of CML can therefore be heterogeneous with respect to cellular expression and in a significant proportion of patients involves a cell which is by membrane markers and morphological criteria indistinguishable from that seen in the common form of ALL. In these cases the Philadelphia chromosome may be the only distinguishing cellular characteristic.

Cell Transformation, Neoplastic↗

Detection of monocyte specific antigen on human acute leukaemia cells.

Heteroantisera with specificity for human monocyte and macrophage antigens (HuMa) have been tested for activity against peripheral blood cells from patients with acute leukaemia. Using indirect immunofluorescence, blast cells from 25/27 patients with acute myelomonocytic leukaemia were reactive with anti-HuMa antisera, whereas blasts from 19/20 patients with acute myeloblastic leukaemia and 13/13 patients with acute lymphoblastic leukaemia were not reactive. The F(ab1)2 fragment of the antibody retained specific activity. Activity of whole serum against myelomonocytic blast cells was specifically removed by absorption with macrophages. These observations indicate that circulating blast cells from patients with acute myelomonocytic leukaemia may carry differentiation antigens characteristic of monocytes and macrophages.

Animals↗

Differential expression of cell surface binding sites for cholera toxin in acute and chronic leukaemias.

Binding of purified cholera toxin to cell surface receptors has been visualized by an indirect immunofluorescence procedure. Normal nucleated cells from blood, bone marrow and lymphoid tissues, express these receptors with the possible exception of erythroid precursors. Cells from patients with chronic lymphoid or myeloid leukaemias have a normal receptor expression but acute leukaemic cells showed a marked deficiency in cholera toxin binding. Insertion of purified Gm ganglioside into membranes of acute leukaemic cells provided cellular binding sites for the toxin.

Bacterial Toxins↗

Virus 'receptors' on lymphocytes.

This paper gives a review of the field of virus-lymphocyte interactions and virus receptors on lymphocytes as well as the use of viruses as markers for various lymphocyte populations.

Animals↗