Thousands of people in the United States are diagnosed each year with PV or ET, blood cancers that cause an excess of red blood cells (PV) or blood-clotting platelets (ET). Itching, headaches, weight loss, tiredness, and night sweats are common complaints among patients.
Although current therapies can generally manage elevated blood counts, they don’t offer much respite from the often severe symptoms, which may have a big effect on one’s quality of life.
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A study, led by Dr Martin Zeidler of the University of Sheffield’s Department of Biomedical Science and Dr Sebastian Francis from the Department of Haematology at the Royal Hallamshire Hospital, found that methotrexate (MTX), commonly used to treat rheumatoid arthritis, significantly reduces the symptoms associated with the disease.
Based on previous Medical Research Council-funded work in the Zeidler lab that detected methotrexate as an inhibitor of the JAK/STAT signalling pathway, this study analyzed hospital records to find existing ET and PV patients already taking methotrexate for other diseases.
Despite the limited numbers involved and the presence of background rheumatoid arthritis, these individuals reported substantially less symptoms than those who were not on methotrexate.
The misregulation of the JAK/STAT signalling pathway in humans is central to the development of Myeloproliferative neoplasms (MPNs), the collective term for progressive blood cancers like ET and PV and is also central to many inflammatory processes such as those associated with rheumatoid arthritis.
Lab-based results showed that low doses of methotrexate acted as a powerful suppressor of JAK/STAT pathway activation — even in cells carrying the mutated gene responsible for MPNs in patients.
Dr Zeidler said:
“While we still need to undertake a clinical trial to validate these findings, our results are very encouraging and suggest that a simple drug that has been used for nearly 40 years to treat arthritis can provide significant relief to blood cancer sufferers.
“Patients we tested showed a pronounced improvement in symptoms, something conventional treatments have been unable to provide.
“Given the very low cost of MTX, this research could offer an effective therapy on a budget accessible to healthcare systems throughout the world — marking a potentially substantial clinical and health economic benefit.”
An 81-year-old PV patient based in California commented: “Methotrexate seemed to do a very nice job of controlling itching and night sweats. My subjective experience of MTX was of a PV holiday.”
MTX has been used for 40 years to treat inflammatory diseases including rheumatoid arthritis, Crohn’s disease and psoriasis.
Even though the mechanisms by which MTX acts in these diseases had not previously been understood, the safety and effectiveness of MTX is well documented and many millions of patients regularly take the drug.
Diseases such as rheumatoid arthritis all feature inflammatory processes driven by JAK/STAT activity and the effectiveness of MTX in these inflammatory diseases may well be a consequence of its ability to dampen the JAK/STAT pathway.
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