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Biomedical subjects

M F Greaves

Publications and source records attributed to M F Greaves.

At least 37 records · Page 2Linked to original sources

Lymphoid blast crisis in chronic myeloid leukaemia and Philadelphia positive acute lymphoid leukaemia.

Membrane markers (anti-ALL and anti-Ia antisera) and an enzyme marker (terminal transferase) have been used to define an L-type or "lymphoid" type of acute transformation in chronic myeloid leukaemia and Ph1 positive acute leukaemia. Patients with L-type ("lymphoid") blasts responded to regimens including vincristine and prednisolone (VP). The markers showed better correlation with survival than did the morphology of blasts. The clinical course of patients was variable; elimination Ph1 positive clone (and hypoplasia), return to the chronic phase and relapses (including meningeal leukaemia) were observed. In contrast, patients with myeloid blasts ("M" type of blast crisis) failed to respond to vincristine and prednisolone.

Antineoplastic Agents

Acid-phosphatase reaction in acute lymphoblastic leukaemia.

The diagnostic value of the acid-phosphatase reaction was assessed double-blind in 148 cases of acute lymphoblastic leukaemia (A.L.L.) classified by surface-membrane markers and entered into the M.R.C. U.K. A.L.L. trials. 90% of cases of T-A.L.L. showed a positive reaction in the majority of blast cells, while only 2% of common-A.L.L. and 10% of null-A.L.L. were positive. This cytochemical reaction distinguished the more aggressive form of A.L.L. any may aid the choice of therapy.

Acid Phosphatase

Expression of hexosaminidase isoenzymes in childhood leukemia.

Because differences in hexosaminidase isoenzyme profiles of granulocytes and lymphoyctes suggested that such profiles might help to distinguish between various types of leukemia, was examined leukocyte extracts from 55 untreated children and 12 controls by automated anion-exchange chromatography. In 23 of 27 cases of the common form of childhood acute lymphoblastic leukemia, the activity of hexosaminidase component I was greatly increased; the activity ratio of hexosaminidase I to hexosaminidase A was greater than 0.5 in 18 of these cases, whereas for other types of leukemia and for all normal cells tested, the ratio was less than 0.2. A raised hexosaminidase I was shown to be associated with leukemic cells by the finding of normal isoenzyme profiles of bone-marrow cells from 17 patients in remission who had such an increase either at diagnosis or in relapse. Hexosaminidase isoenzyme analysis had diagnostic value and may provide a new marker for study of leukocyte differentiation.

Adult

Maturation linked expression of a myeloid cell surface antigen.

An antiserum raised against myelomonocytic and monocytic leukaemia cells has been used to define a cell surface antigen shared by normal and leukaemic cells of the granulocyte and monocyte cell lines. The quantitative expression of this antigen was investigated using the Fluorescence Activated Cell Sorter and was shown to correlate with the degree of morphological maturation.

Animals

Independent mobility of cholera toxin binding sites and Thy-1 alloantigen on mouse thymocytes.

The hypothesis that Thy-1.2 carries a carbohydrate antigenic determinant with the same specificity as the monosialoganglioside GM1 was tested by attempting to co-cap Thy-1.2 and GM1 in CBA thymocytes using anti-Thy-1.2 alloantiserum and cholera toxin. Co-capping of these determinants was not observed suggesting that they are on separate molecules. We do not therefore confirm the previous reported association between Thy-1 and GM1 (Thiele, Arndt & Stark, 1977).

Animals

Terminal deoxynucleotidyl-transferase levels and membrane phenotypes in diagnosis of acute leukaemia.

Terminal deoxynucleotidyl transferase (T.D.T.) has been measured in the cells of 112 leukaemia patients whose cells were characterised by membrane markers as well as by standard haematological and cytochemical criteria. The concentration of enzyme ranged from 0.1 to 1.4 units/10(8) cells in the bone-marrows of 20 patients with normal marrow or benign marrow hyperplasia. The enzyme level was raised in 30 of 31 patients with untreated acute lymphoblastic leukaemia (A.L.L.) whose cells reacted positively with an anti-A.L.L. serum (range 0.9-197, mean 59, units/10(8) cells) and in all 9 patients with thymic A.L.L. (Thy-A.L.L.) (range 1.5-95, mean 36, units/10(8) cells). All but 1 of 17 patients with acute myeloblastic leukaemia gave negative results (range 0-1.5, mean 0.60, units/10(8) cells), and T.D.T. was also normal in all 7 bone-marrow samples from patients with chronic granulocytic leukaemia (C.G.L.) in the chronic phase. The T.D.T. assay gave a clear distinction between 11 patients with C.G.L. in lymphoid transformation, anti-A.L.L.-serum positive (range 15-226, mean 83, units/10(8) cells), and 12 patients with C.G.L. in myeloblastic transformation, anti-A.L.L.-serum negative (range 0-1.9, mean 0.7, units/10(8) cells). Among 17 patients with otherwise unclassifiable acute leukaemia, 10 gave raised values (range 1.6-113 units/10(8) cells) and 7 gave normal values. It is concluded that the assay of T.D.T. in the peripheral blood or bone-marrow of patients with acute leukaemia is of value in differentiating lymphoid (including non-T non-B and Thy-A.L.L.) from myeloid leukaemia.

Biomarkers, Tumor

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