Antidepressant Teams up Against Leukemia

Acute myeloid leukemia responds to ATRA and TCP

/ Author:  / Reviewed by: Joseph V. Madia, MD

(RxWiki News) Vitamin A derivatives, drugs known as retinoids, have been used successfully to treat certain types of leukemia. Not all forms of the disease respond to them, though. Scientists have discovered that adding another medication may overcome this resistance.

A particularly lethal form of leukemia - acute myeloid leukemia (AML) - appears to regress when a retinoid called all-trans retinoic acid (ATRA) is combined with an antidepressant known as tranylcypromine (TCP).

"Ask your oncologist about combination therapies."

ATRA is a chemotherapy agent that has been used to treat a rare form of acute myeloid leukemia, but the drug doesn't work on the more common types of the disease.

A team of researchers at the Institute of Cancer Research (ICR) has been trying to find ways of using retinoids to treat these common forms of AML, and this antidepressant, which is marketed under the brand name Parnate, may be the answer they've been looking for.

"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," said team leader, Arthur Zelent, Ph.D.

What Zelent and his colleagues discovered is that the genes that ATRA targets somehow are switched off, and the antidepressant actually switches it back on, at which point it responds to the medication.

"This new treatment approach may finally make a difference in AML, particularly for those patients who are too old to receive bone marrow transplant or intensive chemotherapy (people over 55-60 depending on the overall health)," Zelent told dailyRx in an email.

A phase II clinical trial to test the combination therapy in AML patients has been started in Germany.

ICR's Kevin Petrie, Ph.D., a study co-author, points out that AML is often fatal and finding a treatment for this difficult cancer is needed - " so it is particularly pleasing to have identified this new treatment approach."

A paper describing this research was published March 11, 2012 in Nature Medicine.

This study was funded primarily by Leukaemia Lymphoma Research and in small part also by the Samue Waxman Cancer Research Foundation.

One person involved with this study declared an association with Progen pharmaceuticals. 

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Review Date: 
March 20, 2012
Last Updated:
November 8, 2012