This study examines the sequential expression of membrane and cytoplasmic characteristics during the early, intermediate and terminal cellular stages of myeloid differentiation. Membrane receptors are examined by resetting techniques, using optimally-sensitised (IgG or C3b) ox erythrocytes, membrane antigens demonstrated by indirect immunofluorescence and cytoplasmic enzymes are characterised by both cytochemical and electrophoretic techniques. In the initial part of the study, leukaemic blast cells are employed as models for early myeloid differentiation and the synthesis of membrane receptors and antigens related to cytoplasmic enzyme expression. In particular, this study investigates the cellular changes associated with monocytic and granulocytic commitment and furthermore assesses, following chromatographic fractionation, the properties of cytoplasmic alpha naphthyl acetate esterases (ANAE) produced by these cell lines. The second part of the study details the expression of Fc-IgG and C3b membrane receptors by developing bone marrow granulocytes in normal and haematologically abnormal disorders. In addition, the relationships between receptor expression and the morphological features of granulocytic differentiation are assessed and abnormalities of receptor expression related to aberrant or asynchronous phenotypic maturation. The final section of the study deals with the normal maturational development of membrane Fc-IgG and C3b receptors and cytoplasmic alkaline phosphatase during the terminal stages of granulocytic differentiation. Relationships with neutrophilic segmentation are examined and the normal patterns of expression compared with those obtained from haematological disorders characterised by abnormal granulopoeisis. The results of this study are examined with regard to current concepts of myeloid differentiation.
|Date of Award||1984|