White blood cells in blood smear
Key points:
- Researchers have identified a molecule that can quickly—and briefly—boost white blood cell counts.
- In mice, A485 provoked a strong increase in white blood cells after exposure. About 12 hours later, cell counts dropped back to previous levels.
- Leveraging the molecule in treatment is especially important for immunocompromised cancer patients.
In genetic conditions like severe congenital neutropenia or acquired conditions after chemotherapy treatment, patients suffer from reduced white blood cell counts, a critical part of the body’s immune system. However, there are few pharmacological options for adjusting white blood cells counts in patients with abnormal levels, including those with diseases like leukemia, where white blood cell levels are too high rather than low.
Now, in a new study published in Immunity, researchers have identified a molecule, known as A485, that can quickly and temporarily increase levels of white blood cells. The molecule, which the researchers have proposed calling “prohiberin,” inhibits proteins that modulate gene expression, essentially turning genes on or off.
In mice, A485 provoked a strong increase in white blood cells, deployed from the animals’ bone marrow, shortly after exposure. About 12 hours later, cell counts dropped back to previous levels. This short-term effect is key, the researchers say.
“Currently, the main treatment for low white blood cell counts is G-CSF, or granulocyte colony-stimulating factor, which is produced by the body and can be administered as a drug,” said Nikolai Jaschke, lead author of the study and a postdoctoral fellow at Yale. “But it has a long-lasting effect, which can be harmful in some circumstances, limiting its wider clinical use. A485 is just as potent as G-CSF but less enduring.”
To see if this brief increase in white blood cells might be effective in treating infection, the researchers gave A485 to mice that had received chemotherapy—and, therefore, had damaged bone marrow—and had also been infected by the bacteria listeria. Even with damaged bone marrow, mice that received A485 survived at higher rates than those that did not, as they were able to clear the bacteria more effectively.
A485 works, in part, through endogenous G-CSF, which is a protein that stimulates the bone marrow to make more blood cells. Jaschke and colleagues also found that combining G-CSF and A485 produced an additive effect on white blood cell mobilization. Additionally, A485 activates what’s known as the body’s “stress axis,” engaging a hormone that, until now, was believed to only regulate levels of cortisol.
Going forward studies should test A485 against other infections, Jaschke said, as listeria is not the most common pathogen patients tend to encounter when immunocompromised. Additionally, more research needs to be done to better understand how A485 has the effect that it does.