retinol-palmitate and Leukemia--Promyelocytic--Acute

A 74 year-old woman, who had been diagnosed as AML (M3) in poor condition, was treated with Retinol Palmitate (Chocola-A, 150,000 unit/m2 per os, after informed consent. An increase of white blood cells (neutrophil) counts was observed after 7 days. After 4 weeks, WBC counts were increased to 20,700/microliters (neutrophil counts 6,400/microliters) Maturation tendency of leukemic cells was also proved in the bone marrow. In vitro studies showed that morphological differentiation was recognizable in cultured leukemic cells treated with 10(-6)M all-trans retinoic acid after 6 days, but not in controls. Responses in the NBT reduction test were slightly less than in the clinical study. The administration of Retinol Palmitate may be a new regimen to treat AML (M3) in aged patients in poor condition.

Topics: Administration, Oral; Aged; Cell Differentiation; Diterpenes; Female; Humans; Leukemia, Promyelocytic, Acute; Retinyl Esters; Tumor Cells, Cultured; Vitamin A

Topics: Aged; Bone Marrow; Carbon Radioisotopes; Cell Differentiation; Cell Line; Diterpenes; Female; Glycine; Hematopoietic Stem Cells; Humans; Hypoxanthine; Hypoxanthines; Leukemia, Promyelocytic, Acute; Monocytes; Phenotype; Purine Nucleosides; Retinyl Esters; Tumor Cells, Cultured; Vitamin A

A 67-year-old woman with acute promyelocytic leukemia (APL) showed a marked decrease in leukemic promyelocytes with concomitant maturation of leukemic cells during treatment with retinol palmitate. A culture study in vitro revealed that retinol, which is the main metabolite of retinol palmitate detected in plasma, induced morphological and functional maturation of leukemic promyelocytes. These findings may indicate that retinol palmitate induces cell differentiation and slows proliferation of leukemic cells in vivo, and that the reduction in cell growth is the key phenomenon in the clearing of leukemic cells, rather than the maturation phenomenon itself.

Topics: Aged; Antineoplastic Agents; Bone Marrow; Cell Division; Diterpenes; Female; Humans; Leukemia, Promyelocytic, Acute; Retinyl Esters; Vitamin A

Newly absorbed retinol is transported in association with chylomicrons and their remnants. In addition, after intake of high doses of retinol, significant amounts are also found in low-density lipoprotein (LDL). As both chylomicron remnants and LDL may be taken up by cells via the LDL receptor, and retinoids inhibit proliferation of some leukaemic cells, we have studied the uptake of retinol in leukaemic cells via the LDL-receptor pathway. HL-60 cells contain saturable binding sites for LDL. The binding of LDL to its receptor has a dissociation constant of about 3.2 x 10(-9) M, and the number of receptors per cell was calculated to be about 2700. Uptake of 125I-LDL by HL-60 cells was increased 2-fold by preincubating the cells with mevinolin. The presence of specific receptors for LDL on HL-60 cells was further confirmed by the finding that exogenous LDL cholesterol was able to up-regulate the ACAT (acyl-CoA: cholesterol acyltransferase) activity of HL-60 cells. We then tested the uptake of retinyl ester in leukaemic cells via the LDL-receptor pathway. HL-60 cells were incubated with LDL or chylomicron remnants labelled with [3H]retinyl palmitate. Uptake of retinyl ester associated with both LDL and chylomicron remnants was observed. Furthermore, the presence of excess LDL decreased the uptake by 75-100%, supporting the hypothesis that the uptake of retinyl ester occurred via the LDL receptor in HL-60 cells.

Topics: Cell Line; Diterpenes; Humans; Leukemia, Promyelocytic, Acute; Lipoproteins; Lipoproteins, LDL; Lovastatin; Retinoids; Retinol-Binding Proteins; Retinyl Esters; Sterol O-Acyltransferase; Tumor Cells, Cultured; Vitamin A