How interferon changes cancerous blood stem cells

A new study from Weill Cornell Medicine shows how interferon-alpha affects cancerous blood stem cells

Interferon-alpha is a drug used to treat certain blood cancers; these findings could help researchers develop better treatments for myeloproliferative neoplasms (MPNs).

The study, published in Nature Genetics, shows that interferon-alpha can push mutant blood stem cells to mature rapidly, ultimately reducing the number of cancerous cells in the bone marrow.

Turning stem cells into short-lived immune cells

Blood stem cells are found in the bone marrow and produce the body’s different blood cell types, including red blood cells, platelets, and white blood cells.

In MPNs, mutations in these stem cells can disrupt normal blood production. In essential thrombocythemia, for example, the bone marrow produces excessive numbers of megakaryocytes, the cells responsible for making platelets. This can increase the risk of serious complications such as heart attacks and strokes.

Researchers found that interferon-alpha appears to activate an emergency-like infection response in blood stem cells. The treatment encourages these cells to quickly develop into neutrophils, a type of white blood cell that helps fight infections.

Because neutrophils have relatively short lifespans, repeatedly forcing stem cells down this pathway can gradually reduce the stem-cell population. The researchers found that mutant stem cells were more vulnerable to this effect than healthy, non-mutant cells in patients who responded well to treatment.

Restoring balance in blood production

The researchers also discovered another important effect of interferon-alpha. The treatment encouraged many blood stem cells to produce lymphoid cells, which are another major category of blood cells involved in immune function.

This shift may help correct the imbalance between myeloid and lymphoid blood-cell production that can occur in MPNs.

Interferon-alpha also appeared to suppress gene activity associated with “inflammaging,” the chronic, low-level inflammation that tends to increase with age. This could represent an additional beneficial effect of the treatment.

Creating more targeted cancer treatments

Although interferon-alpha can be effective, its broad effects on the body can cause significant side effects. Understanding exactly how the drug affects cancerous stem cells could therefore help scientists develop treatments that activate its useful mechanisms without triggering as many unwanted effects.

The researchers believe these findings could eventually lead to more selective therapies for MPNs and potentially other blood cancers. Similar approaches may also help with certain precancerous conditions, where eliminating abnormal blood stem cells could prevent disease progression.

The team is continuing to investigate how interferon-alpha works and whether naturally produced interferon-alpha may also contribute to some autoimmune diseases by triggering excessive inflammatory responses.