NUCLEAR ANTIGEN MARKERS IN HUMAN BLOOD CELLS

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The myeloid cell nuclear differentiation antigen (MNDA) is an m/r 55,000 protein that is specifically expressed in human myeloid cells. The significance of the presence or absence of the MNDA in abnormalities of human myeloid cell growth and differentiation will be established. These results will be correlated with the results from standard diagnostic tests and analysis of the ability of abnormal hematopoietic cells to differentiate in vitro with or without added inducers. The nucleus is a location where control over differentiation exists in the cell; therefore, the development of markers of the nuclear status of hematopoietic cells could lead to more reliable diagnosis in hematopathology. A longterm objective of the project is to contribute to the use of new approaches to treating abnormalities of myeloid cell growth and differentiation. Monoclonal antibodies and immunoblotting technology will be used to investigate physical characteristics and the binding properties of the MNDA. These antibodies will also be used in microinjection experiments and in the localization of MNDA at the ultrastructural level. The gene(s) for the MNDA will be cloned and the sequence information will be used to establish homology to other proteins. The MNDA is a low abundance protein in expressing cells and the expression of recombinant protein will be necessary for complete characterization and functional analysis. Additional information on function will be obtained through the development of appropriate gene constructs that will make it possible to express the MNDA protein in cells that do not normally express the MNDA and to inhibit the expression of the MNDA in expressing cells. Probes for the MNDA gene will be used to examine the chromosomal location of the gene and elucidate the regulation of its expression in leukemic cell lines and human hematopoietic neoplasms. The discovery of the MNDA provides a unique opportunity to exploit the presence of a cellspecific nuclear protein as a marker of human myeloid cells and as a tool to investigate mechanisms that may be operating in the nucleus during normal and abnormal myeloid cell differentiation.