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Biochemical characterization of a leukemia-associated inhibitor (LAI) suppressing normal granulopoiesis in vitro

T Olofsson and I Olsson

Low-density (less than 1.077 g/ml) marrow or blood cells from patients with acute or chronic leukemia release a high molecular weight substance called "leukemia-associated inhibitor" (LAI) that reduces the fraction of normal marrow CFU-c in S-phase as measured with the 3H-TdR suicide technique. LAI from conditioned media or 3M KCl extracts of subcellular fractions behaved homogeneously on gel chromatography, showing an apparent molecular weight greater than 500,000. However, ion- exchange chromatography and isoelectric focusing indicated considerable charge heterogeneity for LAI molecules. Results from SDS-polyacrylamide gel electrophoresis indicated that the biologic activity resides in a subunit of 150,000-170,000 daltons. The findings of marked affinity for Con-A-Sepharose, marked susceptibility to mild periodate treatment, partial susceptibility to protease digestion, and relative resistance to heating suggest that LAI is a glycoprotein. Data from radiolabeling of cell surface components and sucrose density gradient centrifugation are consistent with LAI being a peripheral cell membrane glycoprotein, which may suppress normal granulopoiesis in leukemia.

Volume 55, Issue 6, pp. 983-991, 06/01/1980
Copyright © 1980 by The American Society of Hematology


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S. Skold, B. Rosberg, U. Gullberg, and T. Olofsson
A Secreted Proform of Neutrophil Proteinase 3 Regulates the Proliferation of Granulopoietic Progenitor Cells
Blood, February 1, 1999; 93(3): 849 - 856.
[Abstract] [Full Text] [PDF]



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  Copyright © 1980 by American Society of Hematology         Online ISSN: 1528-0020