The goals are to use the unique dye merocyanine 540 (MC540) to study the architecture of hematopoietic cell membranes, to examine the relationship between leukemia cells and their normal cell counterparts, and to explore its application in the detection, diagnosis, and treatment of certain leukemias. Merocyanine 540 (MC540) is a fluorescent organic molecule that binds specifically to the surfaces of leukemia cells and thereby sensitizes them to photolysis. Because specificity of the dye crosses both lineage and species boundaries, it must identify some feature fundamental to all leukemia cells. In fact, binding studies with artificial lipid vesicles and model erythrocytes have shown it to bind specifically to membranes in which the lipids are loosely packed. Functionally, MC540-binding membranes are involved in receptor elimination via enucleation in erythroid cells, endocytosis in macrophages, and possibly receptor elimination or activation in lymphocytes. The discovery that erythrocytes of patients with chronic myelogenous leukemia (CML) stain with MC540 offers a simple system in which to pursue the molecular defect responsible for staining of not only these cells, but also leukemic granulocytes because of their common origin in a defective stem cell, and may also prove a useful criterion with which to follow the course of CML in a clinical setting. Preliminary results indicate that MC540 can identify not only erythrocytes from patients with CML but also erythrocytes from patients with any of the other myeloproliferative diseases we have tested: polycythemia vera, myelofibrosis, with myeloid metaplasia, essential thrombocythemia and certain forms of acute myelogenous leukemia. Therefore, staining of erythrocytes with MC540 could provide a simple blood test for the detection of myeloproliferative diseases in general. (3)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA028921-05A1
Application #
3168402
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1981-07-01
Project End
1988-05-31
Budget Start
1985-08-01
Budget End
1986-05-31
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Type
Schools of Arts and Sciences
DUNS #
City
University Park
State
PA
Country
United States
Zip Code
16802
Verhoven, B; Schlegel, R A; Williamson, P (1992) Rapid loss and restoration of lipid asymmetry by different pathways in resealed erythrocyte ghosts. Biochim Biophys Acta 1104:15-23
Antia, R; Schlegel, R A; Williamson, P (1992) Binding of perforin to membranes is sensitive to lipid spacing and not headgroup. Immunol Lett 32:153-7
Williamson, P; Kulick, A; Zachowski, A et al. (1992) Ca2+ induces transbilayer redistribution of all major phospholipids in human erythrocytes. Biochemistry 31:6355-60
Pradhan, D; Williamson, P; Schlegel, R A (1991) Bilayer/cytoskeleton interactions in lipid-symmetric erythrocytes assessed by a photoactivable phospholipid analogue. Biochemistry 30:7754-8
Fujimagari, M; Williamson, P L; Schlegel, R A (1990) Ca2(+)-dependent membrane-binding proteins in normal erythrocytes and erythrocytes from patients with chronic myelogenous leukemia. Blood 75:1337-45
Williamson, P; Puchulu, E; Westerman, M et al. (1990) Erythrocyte membrane abnormalities in sickle cell disease. Biotechnol Appl Biochem 12:523-8
Pradhan, D; Weiser, M; Lumley-Sapanski, K et al. (1990) Peroxidation-induced perturbations of erythrocyte lipid organization. Biochim Biophys Acta 1023:398-404
Pradhan, D; Williamson, P; Schlegel, R A (1989) A photoactivable phospholipid analogue that specifically labels membrane cytoskeletal proteins of intact erythrocytes. Biochemistry 28:6943-9
Tullius, E K; Williamson, P; Schlegel, R A (1989) Effect of transbilayer phospholipid distribution on erythrocyte fusion. Biosci Rep 9:623-33
Del Buono, B J; White, S M; Williamson, P L et al. (1989) Plasma membrane lipid organization and the adherence of differentiating lymphocytes to macrophages. J Cell Physiol 138:61-9

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