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Anticancer drugs

Epigenetic reprogramming sensitizes leukaemia to drug treatment

Nature Reviews Drug Discovery volume 11, pages 352–353 (2012)Cite this article

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A paper in Nature Medicine shows that inhibitors of an enzyme involved in the epigenetic regulation of gene expression — lysine-specific demethylase 1 (LSD1; also known as KDM1A) — can make drug-insensitive forms of acute myeloid leukaemia (AML) responsive to treatment with all-trans-retinoic acid (ATRA).

To test this possibility, they first treated AML cells with theLSD1 inhibitors trans-2-phenylcyclopropylamine (TCP) and compound 2d (a biguanide polyamine analogue) in combination with ATRA. In AML cells that were ATRA-responsive (HL-60 cells) and ATRA-insensitive (TEX cells), and also in primary non-APL AML samples, combination treatment increased the fraction of cells expressing the myeloid differentiation marker CD11B, whereas treatment with single agents had only a limited effect. Further in vitro studies showed that the combination of ATRA and TCP was more effective at reducing the survival and proliferation of HL-60 cells than treatment with single agents.

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ORIGINAL RESEARCH PAPER

  1. Schenk, T. et al. Inhibition of the LSD1 (KDM1A) demethylase reactivates the all-trans-retinoic acid differentiation pathway in acute myeloid leukemia. Nature Med. 18, 605–611 (2012)

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  1. Charlotte Harrison
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Harrison, C. Epigenetic reprogramming sensitizes leukaemia to drug treatment. Nat Rev Drug Discov 11, 352–353 (2012). https://doi.org/10.1038/nrd3729

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