Hemin control of heme biosynthesis and catabolism in a human leukemia cell line.
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Biomedical subjects
Publications and source records attributed to M J Murnane.
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The ability of cells derived from the K562 cell line to generate erythropoietic colonies was studied. The K562 cell line was derived from a patient with chronic myelogenous leukemia 8 yr ago by Lozzio and Lozzio. Rare benzidine-positive colonies formed when these cells were cloned in plasma clots (3 +/- 1/10(4) cells), and their number was not substantially increased by the addition of erythropoietin (9.5 +/- 1/10(4) cells). Sodium butyrate was capable of markedly enhancing the number of benzidine-positive colonies (19.5 +/- 1/10(4) cells) formed, while the combination of sodium butyrate plus erythropoietin exerted a synergistic effect on erythropoietic colony formation (57 +/- 4/10(4) cells). The K562 cell line is a long-term culture system that contains human erythropoietic stem cells. This cell line should be useful in future studies on the cellular and molecular events associated with human erythroid cell differentiation.
The techniques of somatic cell genetics have been used to establish the linkage relationships of loci coding for two forms (A and B) of hexosaminidase (EC 3.2.1.30; 2-acetamido-2-deoxy-beta-D-glucoside acetamidodeoxyglucohydrolase) and to determine whether a structural relationship exists between these forms. In a series of human-mouse hybrid cell lines, hexosaminidase A and B segregated independently. Our results and those reported by other investigators are used to analyze the proposed structural models for hexosaminidase. We have also been able to establish a syntenic relationship between the gene locus responsible for the expression of hexosaminidase A and those responsible for mannosephosphate isomerase and pyruvate kinase-3 and to assign the gene for hexosaminidase B to chromosome 5 in man. There is thus a linkage between specific human autosomes and enzymes implicated in the production of lipid storage diseases.
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Clinicopathologic staging of colorectal cancers cannot always predict aggressiveness of prognosis for a particular patient. We have used activity assays for cysteine proteinases, cathepsins B, L and H (CB, CL and CH) and matrix metalloproteinases, MMP-2 and MMP-9, to identify several distinctive, reproducible proteolytic profiles in a large set of colorectal carcinomas. We observed that individual proteinases demonstrated specific and distinct levels of activity at different cancer stages, possible reflecting non-random steps in a proteolytic cascade related to tumor development. We also observed that individual colon cancers fell into relatively few categories when characterized for the combined expression of three proteinases: CB, CL and MMP-9. Four proteolytic profiles, designated "Early", "Middle", "Late", and "High", could be used to define almost 80% of the colorectal carcinomas analyzed. Such profiles, based on the expression of several proteinases in a given tumor, provided information independent of clinical stage and may identify crucial variations in tumor behavior.