Researchers at Weill Cornell Medicine have identified ways interferon-alpha changes mutant blood stem cells in patients with a type of blood cancer, offering a possible path toward more targeted treatments. The findings describe a biological mechanism; they do not establish a new therapy or show that patients should change their care.
The study, published Sept. 15 in Nature Genetics, focused on essential thrombocythemia, a myeloproliferative neoplasm that can cause excess production of platelets. Interferon-alpha already benefits some patients, but its broad effects can also cause significant side effects, according to the researchers.
The team profiled thousands of individual blood cells from consenting patients before and after treatment. It compared gene activity, surface proteins and other characteristics in cells carrying disease-linked mutations with those in nonmutant cells from the same samples.
Essential thrombocythemia involves overproduction of platelet-making cells, raising the risk of heart attack and stroke. Blood stem cells normally produce several kinds of cells, including red cells, platelet-producing cells and white cells of the immune system.
Two changes in cell development
One observed response to interferon-alpha resembled an emergency reaction to infection. Blood stem cells were pushed to mature into neutrophils, infection-fighting white blood cells that do not live long, reducing the stem-cell population over time.
In patients who responded to treatment, mutant stem cells appeared more susceptible to that process than nonmutant cells. The distinction could help explain why interferon can deplete disease-linked cells rather than simply reducing all stem cells in the same way.
The team also found that treatment steered many blood stem cells toward the lymphoid lineage, helping rebalance populations of immune cells. Interferon suppressed certain gene programs associated with chronic inflammation and aging, the researchers reported.
Possibilities, not a new prescription
Senior author Dr. Anna Nam said the findings may guide efforts to develop more selective approaches for myeloproliferative neoplasms and possibly other blood cancers. That is a research direction, not evidence that a proposed targeted drug has been tested successfully in patients.
The study's single-cell measurements illuminate how an existing treatment can act in the sampled patients. They do not establish that the same response occurs in every patient or that the identified cellular changes alone predict an individual's clinical outcome.
Nam's laboratory is also examining whether naturally occurring interferon-alpha may contribute to some autoimmune conditions through a similar inflammatory response. That separate question remains under investigation, the university said.
The work received support from several research funders, including the National Institutes of Health and the National Cancer Institute. Patients with questions about interferon or their own treatment should consult their clinical team rather than treat these early mechanistic findings as medical instructions.
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