User login
Photo courtesy of the
National Cancer Institute
Preclinical research suggests the antineoplastic agent methotrexate (MTX) could be used to treat patients with myeloproliferative neoplasms (MPNs).
Experiments in Drosophila and human cell lines showed that MTX reduces JAK/STAT pathway activity and MPN-associated pathway signaling.
Researchers therefore speculated that low doses of MTX might treat MPNs as effectively as the JAK1/2 inhibitor ruxolitinib, but for a lower cost.
“Given that a year’s course of low-dose MTX costs around £30, the potential to repurpose MTX could provide thousands of patients with a much-needed treatment option and also generate substantial savings for healthcare systems,” said study author Martin Zeidler, DPhil, of The University of Sheffield in the UK.
He and his colleagues noted that, in comparison, ruxolitinib costs more than £40,000 per year per patient.
The researchers made this comparison and described their work with MTX in PLOS ONE.
The team used cells from the fruit fly Drosophila to screen for small molecules that suppress the JAK/STAT signaling pathway, which is central to the development of MPNs in humans. The screen suggested that MTX and a related molecule, aminopterin, suppress STAT activation.
So the researchers conducted experiments in human cell lines and found that MTX suppresses human JAK/STAT signaling without affecting other phosphorylation-dependent pathways.
The team also found that MTX significantly reduces STAT5 phosphorylation in cells expressing JAK2 V617F. However, MTX-treated cells can still respond to physiological levels of erythropoietin.
The researchers are now looking to undertake clinical trials to examine the possibility of repurposing low-dose MTX for the treatment of MPNs.
“We have the potential to revolutionize the treatment of this group of chronic diseases—a breakthrough that may ultimately represent a new treatment option able to bring relief to both patients and health funders,” Dr Zeidler said. 
Photo courtesy of the
National Cancer Institute
Preclinical research suggests the antineoplastic agent methotrexate (MTX) could be used to treat patients with myeloproliferative neoplasms (MPNs).
Experiments in Drosophila and human cell lines showed that MTX reduces JAK/STAT pathway activity and MPN-associated pathway signaling.
Researchers therefore speculated that low doses of MTX might treat MPNs as effectively as the JAK1/2 inhibitor ruxolitinib, but for a lower cost.
“Given that a year’s course of low-dose MTX costs around £30, the potential to repurpose MTX could provide thousands of patients with a much-needed treatment option and also generate substantial savings for healthcare systems,” said study author Martin Zeidler, DPhil, of The University of Sheffield in the UK.
He and his colleagues noted that, in comparison, ruxolitinib costs more than £40,000 per year per patient.
The researchers made this comparison and described their work with MTX in PLOS ONE.
The team used cells from the fruit fly Drosophila to screen for small molecules that suppress the JAK/STAT signaling pathway, which is central to the development of MPNs in humans. The screen suggested that MTX and a related molecule, aminopterin, suppress STAT activation.
So the researchers conducted experiments in human cell lines and found that MTX suppresses human JAK/STAT signaling without affecting other phosphorylation-dependent pathways.
The team also found that MTX significantly reduces STAT5 phosphorylation in cells expressing JAK2 V617F. However, MTX-treated cells can still respond to physiological levels of erythropoietin.
The researchers are now looking to undertake clinical trials to examine the possibility of repurposing low-dose MTX for the treatment of MPNs.
“We have the potential to revolutionize the treatment of this group of chronic diseases—a breakthrough that may ultimately represent a new treatment option able to bring relief to both patients and health funders,” Dr Zeidler said.
Photo courtesy of the
National Cancer Institute
Preclinical research suggests the antineoplastic agent methotrexate (MTX) could be used to treat patients with myeloproliferative neoplasms (MPNs).
Experiments in Drosophila and human cell lines showed that MTX reduces JAK/STAT pathway activity and MPN-associated pathway signaling.
Researchers therefore speculated that low doses of MTX might treat MPNs as effectively as the JAK1/2 inhibitor ruxolitinib, but for a lower cost.
“Given that a year’s course of low-dose MTX costs around £30, the potential to repurpose MTX could provide thousands of patients with a much-needed treatment option and also generate substantial savings for healthcare systems,” said study author Martin Zeidler, DPhil, of The University of Sheffield in the UK.
He and his colleagues noted that, in comparison, ruxolitinib costs more than £40,000 per year per patient.
The researchers made this comparison and described their work with MTX in PLOS ONE.
The team used cells from the fruit fly Drosophila to screen for small molecules that suppress the JAK/STAT signaling pathway, which is central to the development of MPNs in humans. The screen suggested that MTX and a related molecule, aminopterin, suppress STAT activation.
So the researchers conducted experiments in human cell lines and found that MTX suppresses human JAK/STAT signaling without affecting other phosphorylation-dependent pathways.
The team also found that MTX significantly reduces STAT5 phosphorylation in cells expressing JAK2 V617F. However, MTX-treated cells can still respond to physiological levels of erythropoietin.
The researchers are now looking to undertake clinical trials to examine the possibility of repurposing low-dose MTX for the treatment of MPNs.
“We have the potential to revolutionize the treatment of this group of chronic diseases—a breakthrough that may ultimately represent a new treatment option able to bring relief to both patients and health funders,” Dr Zeidler said.