Nuclear c-myc protein, maturation, and cell-cycle status of human haemopoietic cells.

Abstract

Human c-myc protein, p62c-myc, has been quantitated by flow cytometry in the nuclei of normal marrow and peripheral blood cells, and the HL60 cell line. Marrow and peripheral blood cells exhibit nuclear c-myc protein throughout the cell-cycle, at an average level 2-3-fold lower than HL60 cells. In no cells did p62c-myc vary more than 2-fold throughout the cell cycle. A small subset of marrow G0/G1 cells, enriched in early myeloid and blast cell fractions, contained p62c-myc at levels equal to or even exceeding those of HL60. Overall c-myc protein content was higher in myeloid, compared to erythroid and lymphoid marrow fractions. Within the myeloid lineage, the highest average p62c-myc level was present in cells of intermediate maturation, i.e. myelocytes and metamyelocytes. In the erythroid lineage, c-myc protein level was highest in the most immature cells and declined with maturation. Significant amounts of p62c-myc were present in post-mitotic, end-stage neutrophils, but were barely detectable in cycling late erythroblasts or in quiescent lymphocytes and monocytes. HL60 cells, despite c-myc gene amplification and increased gene expression, contain c-myc protein at a level corresponding to promyelocytes in normal human marrow. The virtual absence of p62c-myc in cycling late erythroblasts, and its presence in post-mitotic end-stage granulocytes, suggests that c-myc protein may have functions unrelated to cell proliferation.