MEROCYANINE DYES AS LEUKEMIA SPECIFIC PROBES

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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)