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ABSTRACT All-_trans_ retinoic acid (ATRA) has recently been shown to synergise with the inhibitory effect of interferon alpha (IFN_α_) on the growth of malignant cells isolated from solid

tumors. We investigated whether ATRA could potentiate the inhibitory effects of IFN_α_ 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_α_ or a combination of both molecules and then plated on semi-solid cultures for

colony-forming cell assay. IFN_α_ 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_α_ dramatically potentiated the inhibitory effects of INF_α_ 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_α_plus ATRA showed the presence of

an increased number of BCR-ABL-negative colonies relatively to what was observed with IFN_α_ alone. FISH analysis showed a higher percentage of Ph-negative cells in the ATRA plus IFN_α_

-treated samples, confirming PCR experiments. These results indicate that, _in vitro_, the combination of IFN_α_ and ATRA effectively inhibits CFU-GM colony formation in CML and suggest that

it has a potential interest for the treatment of CML. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS

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Greffe de Moelle, UMR CNRS 5540, and FR60, Université de Bordeaux 2, 146 rue Léo Saignat, Bordeaux, 33076, France FX Mahon, H Chahine, C Barbot, V Pigeonnier, B Jazwiec, J Reiffers & J

Ripoche Authors * FX Mahon View author publications You can also search for this author inPubMed Google Scholar * H Chahine View author publications You can also search for this author

inPubMed Google Scholar * C Barbot View author publications You can also search for this author inPubMed Google Scholar * V Pigeonnier View author publications You can also search for this

author inPubMed Google Scholar * B Jazwiec View author publications You can also search for this author inPubMed Google Scholar * J Reiffers View author publications You can also search for

this author inPubMed Google Scholar * J Ripoche View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT

THIS ARTICLE CITE THIS ARTICLE Mahon, F., Chahine, H., Barbot, C. _et al._ All-_trans_ retinoic acid potentiates the inhibitory effects of interferon α on chronic myeloid leukemia

progenitors _in vitro_. _Leukemia_ 11, 667–673 (1997). https://doi.org/10.1038/sj.leu.2400611 Download citation * Received: 16 October 1995 * Accepted: 20 December 1996 * Issue Date: 01 May

1997 * DOI: https://doi.org/10.1038/sj.leu.2400611 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link

is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * chronic myeloid leukemia * ATRA * IFNα