Targeting stem cells in myeloproliferative disorders
Dr Steven Lane is evaluating a new combination drug therapy for polycythemia vera (PRV). PRV is a rare disorder of the bone marrow, causing overproduction of red blood cells.
The disease belongs to a group of blood cancers known as myeloproliferative neoplasms or MPNs. A gene mutation called JAK2V617F is the most common molecular abnormality found in patients with PRV as well as other MPNs including essential thrombocytosis and chronic idiopathic myelofibrosis.
Dr Lane and his colleagues have developed a laboratory model of PRV with the JAK2V617F mutation. From this model, they have identified a rare stem cell population that initiates the disease and is resistant to current treatments.
However, in research funded by a Leukaemia Foundation Postdoctoral Fellowship (2011-2013), Dr Lane has been evaluating whether treating the stem cells with Interferon alpha (IFN) predisposes these cells to dying.
In addition, he has also found that a new class of drugs that inhibit the Jak2 gene caused the death of PRV cells, but did not eradicate the disease-initiating stem cells.
Curing the disease
In this project, Dr Lane is testing the effects of a combination treatment to target and remove the disease stem cells to cure the disease.
“We’re evaluating the effects of combining Jak2-inhibitors with other treatments on PRV-Jak2 stem cells in cells from patients with polycythemia vera,” said Dr Lane.
“These laboratory experiments will help us to understand the interaction of these combined therapies in treating myeloproliferative neoplasms with the JAK2V617F mutation,” he said.
“In the longer-term, our studies will provide a platform for clinical trials aimed at inducing long-term remission and potentially eradicating the disease in some patients.”