BIOCHEMICAL-CHARACTERIZATION OF A LEUKEMIA-ASSOCIATED INHIBITOR (LAI) SUPPRESSING NORMAL GRANULOPOIESIS INVITRO

  • 1 January 1980
    • journal article
    • research article
    • Vol. 55  (6) , 983-991
Abstract
Low-density (< 1.077 g/ml) marrow or blood cells from patients with acute or chronic leukemia release a high MW substance called leukemia-associated inhibitor (LAI) that reduces the fraction of normal marrow CFU-c [granulopoietic stem cells] in S-phase as measured with the 3H-TdR [thymine deoxyribose] suicide technique. LAI from conditioned media or 3 M KCl extracts of subcellular fractions behaved homogeneously on gel chromatography, showing an apparent MW > 500,000. However, ion-exchange chromatography and isoelectric focusing indicated considerable charge heterogeneity for LAI molecules. Results from SDS[sodium dodecyl sulfate]-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[concanavalin]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.