Researchers at WashU Medicine have identified a possible route to tame inflammation in myeloproliferative neoplasms — a group of chronic blood cancers — that could serve as a novel approach to treatment. The study is led by Stephen Oh, MD, PhD, a professor of medicine who treats these patients at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine.
These cancers progress relatively slowly and cause an ongoing overproduction of blood cells. Many patients experience blood clots and enlarged spleens, and some progress to acute myeloid leukemia, an aggressive form of blood cancer with few treatment options and poor survival. Treatments for myeloproliferative neoplasms reduce symptoms but can’t cure the disease or stop it from progressing.
The study, published in the journal Blood, shows that large amounts of a protein called galectin-1 accelerate inflammation in immune cells called monocytes in blood samples from patients with myeloproliferative neoplasms and in mouse models of the disease. Galectin-1 has been implicated in other types of cancers.
Oh, also co-director of WashU Medicine’s Division of Hematology and a research member at Siteman, and his team also identified signals downstream of galectin-1’s activity that perpetuate the inflammation. They found that interfering with these downstream signals — including a receptor called TLR4 and the signaling pathway it triggers, called NF-kappaB — reversed many of the inflammatory effects in monocytes from patients. They further found that mice modeling MPNs and lacking galectin-1 had milder disease, including lower white blood cell counts and less enlargement of the spleen.
The researchers are continuing to investigate this pathway to identify the best ways to reduce or block galectin-1 and its downstream effects, with the goal of developing new anti-inflammatory therapies for patients with myeloproliferative neoplasms.