New treatment for rare blood cancer after genetic link discovery 

Published:

6 March 2025

Genetic glitch in body’s iron regulation found to play a role in polycythemia vera, a rare blood cancer.

Researchers have discovered a link between a rare cancer in which the body makes too many red blood cells and a genetic glitch that causes iron overload. This has led to the development of a drug that could replace the frequent blood withdrawals that people with this condition must undergo – an arduous process that can lead to chronic fatigue.

Polycythemia vera (PV), the name of this rare cancer, puts people at high risk of heart attack, stroke and blood clots, because the body overproduces red blood cells. People living with PV have to get blood drawn regularly to keep the amount of red blood cells in check. But this further reduces PV patients’ iron levels, which are already low because the body uses most of it for making red blood cells.

A new genetic discovery

People who had two copies of [the faulty genetic] variant had an over 12 times increased risk of having PV.

Dr Victoria Jackson, Walter and Eliza Hall Institute of Medical Research, Australia

A genetic mutation behind PV was discovered decades ago. After looking at genetic differences in all of UK Biobank’s 500,000 participants, researchers have discovered a second ‘misspelled’ gene that plays an important role in the disease.

This second gene influences the production of an important biological component, a protein called hepcidin. It regulates how much iron is available for the body to use. A misspelled version of the gene was previously only known to cause hereditary haemochromatosis, in which the body stores too much iron.

“People who had two copies of [the misspelled genetic] variant had an over 12 times increased risk of having PV,” compared with people who only had only one copy of the glitched gene or didn’t carry it at all, says study team member Victoria Jackson. This suggests that there’s a relationship between iron regulation and PV, explains Cavan Bennett, one of the study’s lead researchers. 

Experimental drug shows promise

It was amazing – this project went from concept to clinical trial in four years.

Dr Cavan Bennett, Walter and Eliza Hall Institute of Medical Research, Australia

In mice with PV, the disease got worse when the animals couldn’t produce hepcidin: the more iron available in the blood to make red blood cells, the worse the cancer became. An experimental medication called Divesiran increased hepcidin production and relieved the symptoms in mice.

Divesiran is now being tested in people living with PV. “It was amazing – this project went from concept to clinical trial in four years,” says Bennett. If further trials are successful, the drug could eliminate the need for PV patients to have blood drawn every few weeks. Because Divesiran leaves the body’s iron stores untouched, it could also alleviate iron-deficiency symptoms such as fatigue.

The sheer number of UK Biobank participants is what made it possible to find the gene in the first place, says Jackson. “When you’ve got a rare disease, you need a lot of people to find anything.”