Differentiation of acute myeloid leukemia (AML) cells with ATRA reduces ¹⁸F-FDG uptake and increases sensitivity towards ABT-737-induced apoptosis

Abstract

Acute myeloid leukemia (AML) is a malignant disease of the bone marrow, comprising various subtypes. We have investigated seven different AML cell lines that showed different sensitivities toward the inducer of apoptosis ABT-737, with IC₅₀ concentrations ranging from 9.9 nM to 1.8 µM. Besides, the AML cell lines revealed distinct differences in ¹⁸F-FDG uptake ranging from 4.1 to 11.0%. Moreover, the Pearson coefficient (0.363) suggests a moderate correlation between ¹⁸F-FDG uptake and the IC₅₀ values of ABT-737. Differentiation of the AML cell lines NB-4 and AML-193 with all-trans-retinoic-acid (ATRA) induced a significant increase in sensitivity towards ABT-737 along with a reduced uptake of ¹⁸F-FDG. Therefore, ¹⁸F-FDG uptake could be predictive on sensitivity to treatment with ABT-737. Furthermore, because differentiation treatment of AML cells using ATRA reduced ¹⁸F-FDG uptake and increased sensitivity towards ABT-737, a combined treatment regimen with ATRA and ABT-737 might be a promising therapeutic option in the future.

Keywords:

• Cancer metabolism
• acute myeloid leukemia
• apoptosis
• ABT-737
• all trans retinoic acid (ATRA)
• ¹⁸F-FDG

Acknowledgements

We thank Birgit Blechert and Stephanie Rott for excellent technical assistance.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Deutsche Forschungsgemeinschaft [SFB 824].