Lipoprotein receptors in acute myelogenous leukemia: failure to detect 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 LDL 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 number is increased in AML cells. The LDL receptor number was assayed by ligand blot with rabbit 125I-labeled beta-very-low-density lipoprotein (beta-VLDL) of transferred, SDS-polyacrylamide-gel-electrophoresis-separated AML cell membranes. Samples from 10 patients, six with AML, one with chronic myelogenous leukemia in blast crisis, and three with acute lymphoblastic leukemia, were investigated. The LDL receptor expression was strongly suppressed in all samples to levels lower than that of normal mononuclear cells. This was despite the fact that cells from one patient with AML of M4 subtype had a 50- to 100-fold higher 125I labeled LDL degradation compared with normal cells. Immunoblots with antibodies against gp330/megalin and the LDL-receptor-related protein (LRP) and ligand blot using 125I-labeled 39-kd receptor-associated protein (RAP) could not detect gp330/megalin or VLDL receptors. The LRP was abundant in AML samples of M4 and M5b subtype, as determined 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 possible that the high degradation of 125I-labeled LDL present in type M4 and M5 AML cells may involve another lipoprotein receptor.
Rudling
M
M
Center for Metabolism and Endocrinology, Department of Medicine, NOVUM, Karolinska Institute at Huddinge University Hospital, Sweden. mats.rudling@cnt.ki.se
Gåfvels
M
M
Parini
P
P
Gahrton
G
G
Angelin
B
B
D000293:Adolescent; D000311:Adrenal Glands / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002417:Cattle; D005260:Female; D026541:Heymann Nephritis Antigenic Complex; D006801:Humans; D015151:Immunoblotting; D007668:Kidney / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D011973:Receptors, LDL / Q000378:metabolism*
D026541:Heymann Nephritis Antigenic Complex; D008562:Membrane Glycoproteins; D011973:Receptors, LDL