Low-density lipoprotein (LDL) receptor activity in human acute myelogenous leukemia cells

The rate of receptor-mediated uptake and degradation of ¹²⁵I-labeled low-density lipoprotein (LDL) was 3-100-fold higher in blood mononuclear cells from 7 patients with acute myelogenous leukemia (AML) as compared with cells from 18 healthy subjects and 21 patients with acute and chronic lymphocytic leukemias, infectious mononucleosis, and nonhematologic malignancies. The rate of cholestrol synthesis from ¹⁴C-acetate was also higher (2-30-fold) in the AML cells. The total rate of input of cholesterol (i.e., the sum of LDL-derived and endogenously synthesized cholesterol) in the AML cells was nine fold higher on the average than in the mononuclear cells from normal subjects. In both the normal and AML cells, more than 90% of the cholesterol input was derived from receptor-mediated degradation of LDL and less than 10% from cholesterol synthesized within the cell. Despite the higher input of cholesterol in the AML cells, the cellular content of cholesterol, as measured by cholesterol:protein protein ratio, was 50% lower than in normal mononuclear cells. These data indicate that the turnover of cellular cholesterol is more rapid in AML cells than in normal mononuclear cells. This enhanced turnover might be due to a more rapid rate of utilizaton of cholesterol for cellular growth or to a more rapid efflux of cellular cholesterol. The resultant depletion of cellullar cholesterol elicits both a higher LDL receptor activity and a higher rate of cholesterol synthesis in these leukemic cells.