Increased cholesterol biosynthesis in leukemic cells from patients with hairy cell leukemia.

Although increased cholesterol synthesis is a feature of many types of human leukemic cells, cells from patients with chronic lymphocytic leukemia have a low cholesterol content and display normal rates of cholesterol synthesis when compared with normal human peripheral blood mononuclear cells (PBMNC). In contrast, Ieukemic cells from patients with hairy cell leukemia (HCL). another chronic B-cell leukemia. have an increased cholesterol content. In these studies we show that HCL cells synthesize ‘4C-cholesterol from ‘4C-acetate precursor in lipoprotein-depleted medium at a rate that is 5-6-fold higher than PBMNC (HCL. 224.4 ± 1 55.7 pmole acetate cholesterol. mean ± SD; PBMNC. 40.0 ± 1 7.5 pmole. p < 0.001 ). The increased rate of cholesterol synthesis in HCL cells by comparison with PBMNC persists despite the presence of 100 pg low density lipoprotein (IDU. although cholesterol synthesis in HCL cells and PBMNC is suppressed 60%-70% under these conditions. suggesting that HCL cells possess a normal LDL receptor mechanism. HCL cells mount a subnormal DNA synthetic response to Con-A when cornpared with PBMNC and also show a significantly lower increase in cholesterol biosynthesis in response to Con-A exposure than do PBMNC. Increased cholesterol synthesis in HCL cells is found in both splenectomized HCL patients