Inhibiting protein to treat myeloproliferative neoplasms shows preclinical promise

Imagine a sink that's overflowing — you could bail water with a cup, or you could just turn off the faucet. For decades, scientists have been trying to bail. Now, researchers at St. Jude Children’s Research Hospital may have found how to turn off the tap.

They discovered that revumenib, a drug already approved by the FDA to treat certain leukemias, can also fight myeloproliferative neoplasms — slow-growing, rare blood cancers that currently have limited treatment options. The findings, published in the journal Cancer Cell, showed remarkable results in mice and offer new hope for patients.

Myeloproliferative neoplasms cause the body to make too many blood cells, which can lead to complications like scarring of the bone marrow, a condition called fibrosis. In their experiments, St. Jude researchers treated mice with revumenib, either alone or combined with standard therapy. They also tested removing the menin gene entirely. In most cases, the mice survived to the end of the study and signs of disease — including fibrosis — disappeared.

"We were surprised to find that menin inhibition produced one of the best preclinical results we've ever seen for myeloproliferative neoplasms," said John Crispino, Ph.D., MBA, director of St. Jude's Division of Experimental Hematology. "We saw very strong activity, extending survival, preventing fibrosis and normalizing blood cell counts."

What makes menin inhibition stand out is how it works. Other treatments targeting these cancers attacked mature blood cells near the end of their development — like bailing water from a overflowing sink. But menin inhibition goes after the earlier source cells, turning off the faucet at its root. The team found no significant side effects in their models.

Because revumenib is already approved for other cancers, this could fast-track the path to human clinical trials. Those trials are the critical next step to test whether the treatment works in actual patients.

"We are really excited that this could make a difference for patients," Crispino said. "Menin inhibition has already been a breakthrough therapy for other aggressive leukemias that we treat at St. Jude every day, so we hope that we can leverage that experience to get this into clinical trials and test it as another agent to potentially help people with myeloproliferative neoplasms."

While the findings are still in the early stages, they represent a promising new direction for a group of diseases that have long been difficult to treat.