Telomerase inhibition by retinoids precedes cytodifferentiation of leukemia cells and may contribute to terminal differentiation

Liang Liu, Joel B. Berletch, Jessica G. Green, Mitchell S. Pate, Lucy G. Andrews, Trygve O. Tollefsbol

Research output: Contribution to journalArticlepeer-review

Abstract

Human promyelocytic leukemia HL60 cells display high telomerase activity, a phenotype related to their immortal status. All-trans retinoic acid (ATRA) is a clinically effective cytodifferentiating agent. To understand the mechanism underlying ATRA-induced cytodifferentiation, we did a kinetic analysis of the role of ATRA in inhibiting telomerase in HL60 cells. Our studies indicate that telomerase inhibition by ATRA occurred relatively early after treatment of HL60 cells due to a rapid decrease in hTERT gene expression. More importantly, however, we found through monitoring the expression of CD11b, a marker for granulocytic differentiation of HL60 cells, that down-regulation of telomerase preceded the differentiation of HL60 cells. These observations suggest that the hTERT gene may be a primary target of ATRA regulation of cellular differentiation and the anti-leukemia activity of ATRA may be mediated by its ability to induce the differentiation of the promyelocytic leukemia cells through down-regulation of the hTERT gene.

Original languageEnglish (US)
Pages (from-to)1003-1009
Number of pages7
JournalMolecular Cancer Therapeutics
Volume3
Issue number8
StatePublished - Aug 2004
Externally publishedYes

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