Differentiation induction of human promyelocytic leukemia cells by acyclic retinoid (polyprenoic acid).

Abstract

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.

• Authors: H Tsurumi, A Tojo, T Takahashi, K Ozawa, H Moriwaki, S Asano, Y Muto
• Journal: International journal of hematology (Int J Hematol) Vol. 59 Issue 1 Pg. 9-15 (Dec 1993) ISSN: 0925-5710 [Print] Japan
• PMID: 8161738 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Tretinoin
• 3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid

Topics

• Adolescent
• Adult
• Cell Differentiation (drug effects)
• Female
• Humans
• Leukemia, Promyelocytic, Acute (pathology)
• Male
• Middle Aged
• Tretinoin (analogs & derivatives, pharmacology)
• Tumor Cells, Cultured