Lipoprotein receptors in acute myelogenous leukemia - Failure to defect increased low-density lipoprotein (LDL) receptor numbers in cell membranes despite increased cellular LDL degradation

The high-affinity degradation of low-density Lipoprotein (LDL) is enhanced 3- to 100-fold in leukemic blood cells from patients with acute myelogenous leukemia (AML), suggesting an increased cellular LDL receptor expression. There are, however, inconsistencies regarding the published properties of L DL receptor regulation in AML cells, and previous data on this are indirect . In the present study the aim was to determine whether the LDL receptor nu mber is increased in AML cells. The LDL receptor number was assayed by liga nd blot with rabbit I-125-labeled beta-very-low-density Lipoprotein (beta-V LDL) of transferred, SDS-polyacry lamide-gel-electrophoresis-separated AML cell membranes. Samples from 10 patients, six with AML, one with chronic my elogenous leukemia in blast crisis, and three with acute lymphoblastic leuk emia, were investigated. The LDL receptor expression was strongly suppresse d in all samples to levels lower than that of normal mononuclear cells. Thi s was despite the fact that cells from one patient with AML of M4 subtype h ad a 50- to 100-fold higher I-125-labeled LDL degradation compared with nor mal cells. Immunoblots with antibodies against gp330/megalin and the LDL-re ceptor-related protein (LRP) and Ligand blot using I-125-labeled 39-kd rece ptor-associated protein (RAP) could not detect gp330/megalin or VLDL recept ors, The LRP was abundant in AML samples of M4 and M5b subtype, as determin ed from both RAP ligand blot and immunoblot using an LRP-specific antibody, It is concluded that LDL receptors are suppressed in AML cells. It is poss ible that the high degradation of I-125-labeled LDL present in type M4 and M5 AML cells may involve another Lipoprotein receptor.