Antidepressant could expand the use of a leukaemia treatment

In collaboration with the Press Association

A common adult form of leukaemia could be treated by a drug derived from vitamin A combined with an antidepressant, according to new lab research.

Adding an antidepressant to a 'retinoid' drug that is already used to treat a small subset of acute myeloid leukaemia (AML) patients could make the drug effective for people with different types of AML.

Retinoids are a class of chemical compounds related chemically to vitamin A.

A retinoid called all-trans retinoic acid (ATRA, also known as tretinoin) is already used to treat acute promyelocytic leukaemia - a rare sub-type of AML.

But this latest research suggests that adding the antidepressant tranylcypromine (TCP) could expand its use to many more patients.

Dr Arthur Zelent, one of the study leaders from The Institute of Cancer Research (ICR), said: "Retinoids have already transformed one rare type of fatal leukaemia into a curable disease. We've now found a way to harness these powerful drugs to treat far more common types of leukaemia.

"Until now, it's been a mystery why the other forms of AML don't respond to this drug. Our study revealed that there was a molecular block that could be reversed with a second drug that is already commonly used as an antidepressant.

ATRA works by encouraging leukaemia cells to mature and die naturally, but the researchers say that the reason many AML patients do not respond to the treatment is because the genes that ATRA normally attacks are switched off by an enzyme called LSD1.

The scientists discovered that using TCP to block this 'off switch' could reactivate these genes, making the cancer cells susceptible to ATRA.

Dr Zelent also said that if the findings can be replicated in patients, then the potential benefits are "enormous". The team has already joined forces with the University of Munster in Germany to start a Phase II clinical trial of the drug combination in AML patients.

The authors commented that both the retinoid ATRA and the antidepressant TCP are already available in the UK and off-patent, so these drugs should not be expensive for the health service.

Martin Ledwick, head information Nurse at Cancer Research UK, said that it was exciting to see new approaches to treatment for AML being developed: "Not all AML patients are suitable for treatments like chemotherapy and bone marrow transplants, and these therapies can be hard to cope with."

"This trial is especially interesting as it helps to explain why a treatment that works in a rare form of AML doesn't work in other types and attempts to get over this problem", he added.

But he cautioned that further research will need to be done to see whether the laboratory results really do improve things for patients with AML.

Copyright Press Association 2012

References

  • Schenk, T. et al. (2012). Inhibition of the LSD1 (KDM1A) demethylase reactivates the all-trans-retinoic acid differentiation pathway in acute myeloid leukemia Nature Medicine DOI: 10.1038/nm.2661