Differentiation induction of human promyelocytic leukemia cells by acyclic retinoid (polyprenoic acid).
Acyclic retinoid (all-trans-3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid) has a slightly different structure from all-trans retinoic acid (ATRA), while it binds cellular retinoic acid-binding protein with a similar binding affinity to that of ATRA. We studied the in vitro efficacy of acyclic retinoid for the differentiation induction of human promyelocyte-derived HL-60 cell line and primary cultured blast cells obtained from 8 patients with acute non-lymphocytic leukemia (ANLL) including 3 acute promyelocytic leukemia (APL) patients. HL-60 cells and ANLL cells were incubated with or without retinoids for 5 days. Acyclic retinoid induced the differentiation of HL-60 cells and APL cells at 10(-6) mol/l, while ATRA induced differentiation at 10(-7) mol/l. These concentrations were well below those that affected cell growth and viability. Although ATRA has an excellent capacity for differentiation induction of HL-60 and APL cells, it is also known to have severe, sometimes fatal, adverse effects, including retinoic acid syndrome. In contrast, acyclic retinoid is reported to have a much wider safety margin than that of ATRA. A clinical trial of acyclic retinoid for the differentiation induction therapy of APL may be worthwhile.
Tsurumi
H
H
First Department of Internal Medicine, Gifu University School of Medicine, Japan.
Tojo
A
A
Takahashi
T
T
Ozawa
K
K
Moriwaki
H
H
Asano
S
S
Muto
Y
Y
D000293:Adolescent; D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects*; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D014212:Tretinoin; C034534:3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid