- A drug used to treat arthritis can be used to treat blood
cancer, finds a study by a research team at the University of Sheffield
- Polycythemia Vera is a type of blood cancer that affects 3,000
people a year
- Arthritis drug could be an affordable and effective treatment
for patients with blood cancer
Polycythemia Vera is a
rare type of blood cancer, which causes an overproduction of Red Blood Cells
(RBCs). Currently, available treatments for Polycythemia Vera do not slow the disease
progression. A research team at the University of Sheffield has discovered that
a commonly used arthritis drug can effectively treat blood cancer.
Arthritis Drug can Treat Rare Type of Blood Cancer
(MTX) is a drug commonly
used to treat arthritis
which is also on the World Health
Organization list of essential medicines. MTX works by directly inhibiting the
molecular pathway responsible for causing disease.
‘Patients with a rare type of blood cancer called Polycythemia Vera can be effectively treated with a commonly used arthritis drug, methotrexate (MTX).’
Dr Martin Zeidler, from
the University of Sheffield's Department of Biomedical Science, along with
colleagues from the Department of Hematology at the Royal Hallamshire Hospital
conducted the study. The study was funded by the Medical Research Council
Initially, tests were
carried out on fruit fly cells to screen for molecules that modulate JAK/STAT
In humans, the
misregulation of JAK/STAT signaling pathway is central to the development of
Myeloproliferative neoplasms (MPNs), which is the collective term for progressive
blood cancers like Polycythemia Vera.
Tests carried out on
human cells showed that the drug MTX acts as a potent suppressor of JAK/STAT
pathway activation. The drug suppressed the JAK/STAT pathway activation even in
cells carrying the mutated gene responsible for Myeloproliferative neoplasms in
The research team also
conducted tests on mice to see the effect of the drug MTX in suppressing
JAK/STAT pathway activation. Dr Zeidler, said, that
the tests on mice were entirely consistent with the cell-based studies.
The findings showed that
low-dose MTX suppressed JAK/STAT pathway activation. It also normalizes both
the raised blood counts and the increase in the sleep size, which is associated
with the disease in the mice.
"We have now shown
pretty conclusively that we can use this approach to treat mouse models of
human Myeloproliferative neoplasms, results which provide a much more tangible
prospect of success in humans," said Dr Zeidler.
has the potential to provide a new, molecularly targeted treatment for MPN
patients within a budget accessible to healthcare systems throughout the world
- a development that may ultimately provide substantial clinical and health
economic benefits," he added.
The research team hopes
to conduct a full clinical trial early next year. The findings of the study are
published in Haematologica
, the journal of the European
Hematology Association and the Ferrata Storti Foundation.
For more than three
decades, methotrexate has been used to treat inflammatory diseases including
rheumatoid arthritis, psoriasis, and Crohn's disease.
The safety and
effectiveness of methotrexate are well documented, and millions of patients
regularly take the drug. However, the mechanism by which methotrexate acts in
inflammatory diseases had not previously been understood.
Diseases such as rheumatoid arthritis
psoriasis feature inflammatory processes driven by JAK/STAT pathway activation.
The effectiveness of methotrexate in inflammatory disease may be a consequence
of its ability to suppress the JAK/STAT pathway activation.
Polycythemia Vera, is a
bone marrow disease characterized by an overproduction of red blood cells. In
patients with Polycythemia Vera, the numbers of white blood cells and platelets
may also be higher than normal. The overproduction of red blood cells results
in very thick blood, which can't flow through small blood vessels. As the blood
is thick, it increases the risk of blood clots, stroke, and heart attack.
Patients with Polycythemia Vera have symptoms like itching, headache, weight
loss, fatigue and night sweats. More than 3,000 people in the UK are diagnosed
with Polycythemia Vera every year.
Facts on Polycythemia Vera:
- Polycythemia Vera occurs more often in men than in women
- Most patients with Polycythemia Vera do not have a family
history of the disease
- It is not diagnosed in people under age 40
- It is often linked to a gene defect called JAK2V617F
- Polycythemia Vera is not curable, but can usually be managed
- Kavitha Chinnaiya, Michelle A Lawson, Sally Thomas, Marie-Therese Haider, Jenny Down, Andrew D Chantry, David Hughes, Antony Green, Jon R Sayers, John A Snowden, Martin P Zeidler. Low-dose methotrexate in myeloproliferative neoplasm models. Haematologica, 2017; haematol.2017.165738 DOI:10.3324/haematol.2017.165738
- Polycythemia Vera FACTS - (https://www.lls.org/sites/default/file/file_assets/FS13_PolycythemiaVera_FactSheet_final5.1.15.pdf)