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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA037097-04
Application #
3174774
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1984-04-01
Project End
1990-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37203
Briggs, J A; Burrus, G R; Stickney, B D et al. (1992) Cloning and expression of the human myeloid cell nuclear differentiation antigen: regulation by interferon alpha. J Cell Biochem 49:82-92
Olinski, R; Briggs, R C; Basinger, M et al. (1992) Effectiveness of chemical agents in removing platinum from DNA isolated from cisplatin-treated HL-60 cells. Acta Biochim Pol 39:327-34
Burrus, G R; Briggs, J A; Briggs, R C (1992) Characterization of the human myeloid cell nuclear differentiation antigen: relationship to interferon-inducible proteins. J Cell Biochem 48:190-202
Gaczynski, M; Briggs, J A; Wedrychowski, A et al. (1990) cis-diamminedichloroplatinum(II) cross-linking of the human myeloid cell nuclear differentiation antigen to DNA in HL-60 cells following 1,25-dihydroxy vitamin D3-induced monocyte differentiation. Cancer Res 50:1183-8
Cousar, J B; Briggs, R C (1990) Expression of human myeloid cell nuclear differentiation antigen (MNDA) in acute leukemias. Leuk Res 14:915-20
Duhl, D M; Gaczynski, M; Olinski, R et al. (1989) Intranuclear distribution of the human myeloid cell nuclear differentiation antigen in HL-60 cells. J Cell Physiol 141:148-53
Hudson, C R; Bellew, T; Briggs, J A et al. (1988) Production and use of rat monoclonal antibodies to the human myeloid cell nuclear differentiation antigen. Hybridoma 7:541-53
Briggs, R C; Casey, S B (1988) A nuclear cAMP binding protein in retinoic acid-treated HL-60 cells. J Cell Physiol 136:198-201
Goldberger, A; Hnilica, L S; Casey, S B et al. (1986) Properties of a nuclear protein marker of human myeloid cell differentiation. J Biol Chem 261:4726-31
Brewer, G; Hnilica, L S; Briggs, R C (1985) Effects of hemin on a lymphoblastoid cell line that expresses the human epsilon- and gamma-globin genes. Mol Cell Biochem 68:11-22