All-trans retinoic acid potentiates the inhibitory effects of interferon alpha on chronic myeloid leukemia progenitors in vitro

Leukemia
F X MahonJ Ripoche

Abstract

All-trans retinoic acid (ATRA) has recently been shown to synergize with the inhibitory effect of interferon alpha (IFN alpha) on the growth of malignant cells isolated from solid tumors. We investigated whether ATRA could potentiate the inhibitory effects of IFN alpha on the proliferation of leukemic progenitors in chronic myeloid leukemia (CML). CD34+ cells from chronic phase, newly diagnosed patients, were incubated in short-term liquid culture with ATRA, IFN alpha or a combination of both molecules and then plated on semi-solid cultures for colony-forming cell assay. IFN alpha was found to inhibit preferentially the generation of late progenitors. ATRA at a concentration of 10(-8) M was found strongly to inhibit CFU-M colonies. Addition of ATRA to IFN alpha dramatically potentiated the inhibitory effects of INF alpha on CFU-GM growth. In the presence of both molecules the inhibition of day 14 CFU-GM from CD34+ cells was lowered to 27 +/- 4% of control. CFU-M colonies were completely inhibited. RT-PCR analysis of the colonies resulting from the action of the combination IFN alpha plus ATRA showed the presence of an increased number of BCR-ABL-negative colonies relatively to what was observed with IFN alpha alone. FISH analys...Continue Reading

Citations

Feb 14, 2002·British Journal of Haematology·Stephen B MarleyMyrtle Y Gordon
Dec 26, 2008·Leukemia Research·Hector MayaniAntonieta Chávez-González
Oct 5, 2001·Expert Opinion on Pharmacotherapy·A ReiterR Hehlmann
Dec 3, 2005·Nature Reviews. Immunology·Michael H KershawPhillip K Darcy
Jan 7, 2004·Nature Reviews. Cancer·Glenn Dranoff
Apr 14, 2018·International Journal of Clinical Oncology·Rintaro SogawaShinya Kimura

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