ENHANCEMENT OF ALL-TRANS-RETINOIC ACID EFFICIENCY IN GRANULOCYTIC DIFFERENTIATION OF HL-60 CELLS BY INCORPORATION INTO LOW-DENSITY-LIPOPROTEIN

All-trans-retinoic acid (ATRA) has been proven to lead to complete rem ission of acute promyelocytic leukemia by inducing differentiation int o granulocytes except when an acquired resistance occurred. High level s of low density lipoprotein (LDL) receptor in cancer cells suggested the use of ATRA incorporated into LDL. 50% of HL-60 cell differentiati on were obtained with 5 nmoles/l of ATRA-LDL compared to 150 moles/l o f ATRA. Maximal differentiation (80%) was reached at 25 nmoles/l and 1 ,000 nmoles/l respectively. This higher efficiency suggests the involv ement of LDL receptor in ATRA-LDL internalization and/or the protectio n of the drug, from eventual catabolism, by LDL particles.